PARP1 (poly[ADP-ribose] polymerase 1, ARTD1) is an abundant ~113 kDa nuclear enzyme that acts as a primary sensor of DNA strand breaks. Its N-terminal zinc fingers (Zn1, Zn2) and Zn3 recognise single- and double-strand breaks and drive a cooperative domain assembly that relieves autoinhibition of the C-terminal catalytic domain (helical subdomain plus ART fold with catalytic Glu988). Activated PARP1 uses NAD+ to transfer ADP-ribose to itself (mainly within its BRCT-containing automodification domain) and to histones and other chromatin proteins, and elongates and branches poly(ADP-ribose) (PAR) chains. Alone it modifies aspartate and glutamate residues; with its accessory factor HPF1, which completes a shared active site, it modifies serine residues (e.g. histone H2B Ser6 and H3 Ser10), the predominant DNA damage-induced mark. PAR recruits repair and chromatin factors such as XRCC1 and ALC1, promoting single-strand break and base excision repair, double-strand break repair and replication-fork responses, while automodification releases PARP1 from DNA; PARP inhibitors trap PARP1 on DNA. PARP1 also binds nucleosomes and modulates chromatin structure and transcription (e.g. NELF and P-TEFb regulation), and cytoplasmic PARP1 can ADP-ribosylate cGAS to restrain innate immune signalling. Excessive activation depletes NAD+ and ATP and generates PAR that triggers AIF (AIFM1) release and caspase-independent cell death (parthanatos). During apoptosis PARP1 is cleaved by caspases-3/7 at Asp214.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000012 single strand break repair | IDA PMID:34102106 XRCC1 prevents toxic PARP1 trapping during DNA base excision... | ACCEPT | Summary: PARP1 senses single-strand breaks and synthesises PAR that recruits XRCC1 and other repair factors, accelerating single-strand break repair; it must then be released from DNA. Reason: Core process. PARP1 directly performs the sensing and signalling step of SSB repair (binding breaks and catalysing PAR synthesis that recruits XRCC1). Supporting Evidence: PMID:34102106 PARPs are sensors that detect single-strand break intermediates, but the critical role of XRCC1 during BER is unknown. PMID:34102106 Consequently, PARP1 deletion rescues BER and resistance to base damage in XRCC1-/- cells. PMID:36323657 Quantitative smFRET and structural ensemble calculations reveal how PARP-1's N-terminal zinc fingers convert DNA SSBs from a largely unperturbed conformation, via an intermediate state into the highly kinked DNA conformation. |
| GO:0000012 single strand break repair | IDA PMID:36323657 Structural dynamics of DNA strand break sensing by PARP-1 at... | ACCEPT | Summary: PARP1 senses single-strand breaks and synthesises PAR that recruits XRCC1 and other repair factors, accelerating single-strand break repair; it must then be released from DNA. Reason: Core process. PARP1 directly performs the sensing and signalling step of SSB repair (binding breaks and catalysing PAR synthesis that recruits XRCC1). Supporting Evidence: PMID:36323657 Quantitative smFRET and structural ensemble calculations reveal how PARP-1's N-terminal zinc fingers convert DNA SSBs from a largely unperturbed conformation, via an intermediate state into the highly kinked DNA conformation. PMID:36323657 Our data suggest an induced fit mechanism via a multi-domain assembly cascade that drives SSB sensing and stimulates an interplay with the scaffold protein XRCC1 orchestrating subsequent DNA repair events. PMID:34102106 PARPs are sensors that detect single-strand break intermediates, but the critical role of XRCC1 during BER is unknown. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:15607977 NAD+-dependent modulation of chromatin structure and transcr... | KEEP AS NON CORE | Summary: PARP1 represses transcription of some genes (chromatin compaction; NF-kappaB targets relieved by caspase-7 cleavage). Reason: Context-dependent transcriptional regulation; non-core. Supporting Evidence: PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. PMID:15607977 Herein, we describe previously uncharacterized nucleosome binding properties of PARP-1 that promote the formation of compact, transcriptionally repressed chromatin structures. PMID:22464733 Here we show that after LPS stimulation, caspase 7 is activated by caspase 1, translocates to the nucleus, and cleaves PARP1 at the promoters of a subset of NF-ΞΊB target genes negatively regulated by PARP1. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:22464733 Inflammasome-activated caspase 7 cleaves PARP1 to enhance th... | KEEP AS NON CORE | Summary: PARP1 represses transcription of some genes (chromatin compaction; NF-kappaB targets relieved by caspase-7 cleavage). Reason: Context-dependent transcriptional regulation; non-core. Supporting Evidence: PMID:22464733 Here we show that after LPS stimulation, caspase 7 is activated by caspase 1, translocates to the nucleus, and cleaves PARP1 at the promoters of a subset of NF-ΞΊB target genes negatively regulated by PARP1. PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | TAS Reactome:R-HSA-2173795 | KEEP AS NON CORE | Summary: PARP1 represses transcription of some genes (chromatin compaction; NF-kappaB targets relieved by caspase-7 cleavage). Reason: Context-dependent transcriptional regulation; non-core. Supporting Evidence: PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. PMID:22464733 Here we show that after LPS stimulation, caspase 7 is activated by caspase 1, translocates to the nucleus, and cleaves PARP1 at the promoters of a subset of NF-ΞΊB target genes negatively regulated by PARP1. |
| GO:0000723 telomere maintenance | TAS PMID:25749521 TNKS1BP1 functions in DNA double-strand break repair though ... | MARK AS OVER ANNOTATED | Summary: Telomere maintenance was attributed to PARP1 by traceable author statement. Reason: The cited paper concerns DSB repair by TNKS1BP1/DNA-PKcs and mentions telomere stability only as a general property of PARP family members; it does not show PARP1 acting in telomere maintenance. Supporting Evidence: PMID:25749521 The TNKS1BP1 protein was demonstrated to interact with DNA-dependent protein kinase (DNA-PKcs) and poly(ADP-ribose) polymerase 1 (PARP-1), by co-immunoprecipitation analysis. |
| GO:0000781 chromosome, telomeric region | HDA PMID:19135898 Purification of proteins associated with specific genomic Lo... | KEEP AS NON CORE | Summary: PARP1 was identified in purified human telomeric chromatin (PICh). Reason: Consistent with general chromatin binding and reported telomere roles; non-core. Supporting Evidence: PMID:19135898 Purification of human telomeric chromatin using PICh identified the majority of known telomeric factors and uncovered a large number of novel associations. |
| GO:0000785 chromatin | IDA PMID:30675909 Increased PARP1-DNA binding due to autoPARylation inhibition... | ACCEPT | Summary: PARP1 binds chromatin, where it modifies histones and can be trapped by PARP inhibitors. Reason: Accepted; consistent with nucleosome binding and chromatin trapping studies. Supporting Evidence: PMID:30675909 PARP1 inhibitors (PARPis) are used clinically during cancer therapy and are thought to exert their cytotoxicity through PARP1 polymerase inhibition and PARP1-DNA trapping. PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. PMID:35013556 We found that following trapping, PARP1 is SUMOylated by PIAS4 and subsequently ubiquitylated by the SUMO-targeted E3 ubiquitin ligase RNF4, events that promote recruitment of p97 and removal of trapped PARP1 from chromatin. |
| GO:0000785 chromatin | IDA PMID:34874266 Serine ADP-ribosylation marks nucleosomes for ALC1-dependent... | ACCEPT | Summary: PARP1 binds chromatin, where it modifies histones and can be trapped by PARP inhibitors. Reason: Accepted; consistent with nucleosome binding and chromatin trapping studies. Supporting Evidence: PMID:34874266 Serine ADP-ribosylation (ADPr) is a DNA damage-induced post-translational modification catalyzed by the PARP1/2:HPF1 complex. PMID:34874266 This chemoenzymatic protein synthesis strategy was employed to assemble a series of full-length, ADP-ribosylated histones and show that ADPr at histone H2B serine 6 or histone H3 serine 10 converts nucleosomes into robust substrates for the chromatin remodeler ALC1. PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. |
| GO:0000785 chromatin | IDA PMID:35013556 The ubiquitin-dependent ATPase p97 removes cytotoxic trapped... | ACCEPT | Summary: PARP1 binds chromatin, where it modifies histones and can be trapped by PARP inhibitors. Reason: Accepted; consistent with nucleosome binding and chromatin trapping studies. Supporting Evidence: PMID:35013556 We found that following trapping, PARP1 is SUMOylated by PIAS4 and subsequently ubiquitylated by the SUMO-targeted E3 ubiquitin ligase RNF4, events that promote recruitment of p97 and removal of trapped PARP1 from chromatin. PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. |
| GO:0001650 fibrillar center | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Human Protein Atlas immunofluorescence localizes PARP1 to nucleolar fibrillar centers. Reason: Consistent with nucleolar localization; sub-nucleolar detail from a single high-throughput source. Non-core. |
| GO:0003677 DNA binding | IDA PMID:21233213 Crystal structures of poly(ADP-ribose) polymerase-1 (PARP-1)... | ACCEPT | Summary: PARP1 is a DNA-binding protein with zinc-finger DNA-binding domains. Reason: Correct though general; PARP1 binds DNA via Zn1/Zn2/Zn3. More specific terms (damaged DNA binding, single-strand break-containing DNA binding) also apply. Supporting Evidence: PMID:21233213 Poly(ADP-ribose) polymerase-1 (PARP-1) has two homologous zinc finger domains, Zn1 and Zn2, that bind to a variety of DNA structures to stimulate poly(ADP-ribose) synthesis activity and to mediate PARP-1 interaction with chromatin. PMID:18055453 Here, we demonstrate using spectroscopic and crystallographic analysis that human PARP-1 has a third zinc-binding domain. |
| GO:0003677 DNA binding | IEA GO_REF:0000002 | ACCEPT | Summary: PARP1 is a DNA-binding protein with zinc-finger DNA-binding domains. Reason: Correct though general; PARP1 binds DNA via Zn1/Zn2/Zn3. More specific terms (damaged DNA binding, single-strand break-containing DNA binding) also apply. Supporting Evidence: PMID:18055453 Here, we demonstrate using spectroscopic and crystallographic analysis that human PARP-1 has a third zinc-binding domain. PMID:21233213 Poly(ADP-ribose) polymerase-1 (PARP-1) has two homologous zinc finger domains, Zn1 and Zn2, that bind to a variety of DNA structures to stimulate poly(ADP-ribose) synthesis activity and to mediate PARP-1 interaction with chromatin. |
| GO:0003677 DNA binding | TAS PMID:2513174 Human nuclear NAD+ ADP-ribosyltransferase(polymerizing): org... | ACCEPT | Summary: PARP1 is a DNA-binding protein with zinc-finger DNA-binding domains. Reason: Correct though general; PARP1 binds DNA via Zn1/Zn2/Zn3. More specific terms (damaged DNA binding, single-strand break-containing DNA binding) also apply. Supporting Evidence: PMID:2513174 Each of the four metal coordinating sites putatively forming the two zinc fingers of the DNA-binding domain is encoded separately. PMID:2513174 The automodification domain and the NAD-binding domain are coded for by 4 and 12 exons, respectively. PMID:18055453 Here, we demonstrate using spectroscopic and crystallographic analysis that human PARP-1 has a third zinc-binding domain. |
| GO:0003682 chromatin binding | IDA PMID:30675909 Increased PARP1-DNA binding due to autoPARylation inhibition... | ACCEPT | Summary: PARP1 binds chromatin, where it is trapped by PARP inhibitors and modifies histones. Reason: Supported by direct chromatin association studies; consistent with nucleosome binding. Supporting Evidence: PMID:30675909 PARP1 inhibitors (PARPis) are used clinically during cancer therapy and are thought to exert their cytotoxicity through PARP1 polymerase inhibition and PARP1-DNA trapping. PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. PMID:35013556 We found that following trapping, PARP1 is SUMOylated by PIAS4 and subsequently ubiquitylated by the SUMO-targeted E3 ubiquitin ligase RNF4, events that promote recruitment of p97 and removal of trapped PARP1 from chromatin. |
| GO:0003682 chromatin binding | IDA PMID:34874266 Serine ADP-ribosylation marks nucleosomes for ALC1-dependent... | ACCEPT | Summary: PARP1 binds chromatin, where it is trapped by PARP inhibitors and modifies histones. Reason: Supported by direct chromatin association studies; consistent with nucleosome binding. Supporting Evidence: PMID:34874266 Serine ADP-ribosylation (ADPr) is a DNA damage-induced post-translational modification catalyzed by the PARP1/2:HPF1 complex. PMID:34874266 This chemoenzymatic protein synthesis strategy was employed to assemble a series of full-length, ADP-ribosylated histones and show that ADPr at histone H2B serine 6 or histone H3 serine 10 converts nucleosomes into robust substrates for the chromatin remodeler ALC1. PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. |
| GO:0003682 chromatin binding | IDA PMID:35013556 The ubiquitin-dependent ATPase p97 removes cytotoxic trapped... | ACCEPT | Summary: PARP1 binds chromatin, where it is trapped by PARP inhibitors and modifies histones. Reason: Supported by direct chromatin association studies; consistent with nucleosome binding. Supporting Evidence: PMID:35013556 We found that following trapping, PARP1 is SUMOylated by PIAS4 and subsequently ubiquitylated by the SUMO-targeted E3 ubiquitin ligase RNF4, events that promote recruitment of p97 and removal of trapped PARP1 from chromatin. PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. |
| GO:0003684 damaged DNA binding | IDA PMID:22683995 The zinc-finger domains of PARP1 cooperate to recognize DNA ... | ACCEPT | Summary: PARP1 zinc fingers recognise damaged DNA (single- and double-strand breaks and other lesions), which activates its catalytic domain. Reason: Damaged-DNA binding is the sensor half of PARP1 core function, demonstrated with purified protein and structural/biophysical studies of break recognition. Supporting Evidence: PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. PMID:22683995 Upon activation at sites of DNA damage, PARP1 modifies itself and other proteins by covalent addition of long, branched polymers of ADP-ribose, which in turn recruit downstream DNA repair and chromatin remodeling factors. PMID:26626479 Poly(ADP-ribose)polymerase 1 (PARP-1) is a key eukaryotic stress sensor that responds in seconds to DNA single-strand breaks (SSBs), the most frequent genomic damage. |
| GO:0003684 damaged DNA binding | IDA PMID:26626479 Structural Basis of Detection and Signaling of DNA Single-St... | ACCEPT | Summary: PARP1 zinc fingers recognise damaged DNA (single- and double-strand breaks and other lesions), which activates its catalytic domain. Reason: Damaged-DNA binding is the sensor half of PARP1 core function, demonstrated with purified protein and structural/biophysical studies of break recognition. Supporting Evidence: PMID:26626479 Poly(ADP-ribose)polymerase 1 (PARP-1) is a key eukaryotic stress sensor that responds in seconds to DNA single-strand breaks (SSBs), the most frequent genomic damage. PMID:26626479 Two flexibly linked N-terminal zinc fingers recognize the extreme deformability of SSBs and drive co-operative, stepwise self-assembly of remaining PARP-1 domains to control the activity of the C-terminal catalytic domain. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0003684 damaged DNA binding | IDA PMID:26626480 PARP-1 Activation Requires Local Unfolding of an Autoinhibit... | ACCEPT | Summary: PARP1 zinc fingers recognise damaged DNA (single- and double-strand breaks and other lesions), which activates its catalytic domain. Reason: Damaged-DNA binding is the sensor half of PARP1 core function, demonstrated with purified protein and structural/biophysical studies of break recognition. Supporting Evidence: PMID:26626480 DNA breaks sharply elevate PARP-1 catalytic activity to mount a cell survival repair response, whereas persistent PARP-1 hyperactivation during severe genotoxic stress is associated with cell death. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. PMID:26626479 Poly(ADP-ribose)polymerase 1 (PARP-1) is a key eukaryotic stress sensor that responds in seconds to DNA single-strand breaks (SSBs), the most frequent genomic damage. |
| GO:0003684 damaged DNA binding | IDA PMID:27568560 JNK Phosphorylates SIRT6 to Stimulate DNA Double-Strand Brea... | ACCEPT | Summary: PARP1 zinc fingers recognise damaged DNA (single- and double-strand breaks and other lesions), which activates its catalytic domain. Reason: Damaged-DNA binding is the sensor half of PARP1 core function, demonstrated with purified protein and structural/biophysical studies of break recognition. Supporting Evidence: PMID:27568560 This post-translational modification facilitates the mobilization of SIRT6 to DNA damage sites and is required for efficient recruitment of poly (ADP-ribose) polymerase 1 (PARP1) to DNA break sites and for efficient repair of DSBs. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. PMID:26626479 Poly(ADP-ribose)polymerase 1 (PARP-1) is a key eukaryotic stress sensor that responds in seconds to DNA single-strand breaks (SSBs), the most frequent genomic damage. |
| GO:0003684 damaged DNA binding | IDA PMID:30675909 Increased PARP1-DNA binding due to autoPARylation inhibition... | ACCEPT | Summary: PARP1 zinc fingers recognise damaged DNA (single- and double-strand breaks and other lesions), which activates its catalytic domain. Reason: Damaged-DNA binding is the sensor half of PARP1 core function, demonstrated with purified protein and structural/biophysical studies of break recognition. Supporting Evidence: PMID:30675909 PARP1 inhibitors (PARPis) are used clinically during cancer therapy and are thought to exert their cytotoxicity through PARP1 polymerase inhibition and PARP1-DNA trapping. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. PMID:26626479 Poly(ADP-ribose)polymerase 1 (PARP-1) is a key eukaryotic stress sensor that responds in seconds to DNA single-strand breaks (SSBs), the most frequent genomic damage. |
| GO:0003684 damaged DNA binding | IDA PMID:32241924 Structural basis for allosteric PARP-1 retention on DNA brea... | ACCEPT | Summary: PARP1 zinc fingers recognise damaged DNA (single- and double-strand breaks and other lesions), which activates its catalytic domain. Reason: Damaged-DNA binding is the sensor half of PARP1 core function, demonstrated with purified protein and structural/biophysical studies of break recognition. Supporting Evidence: PMID:32241924 The success of poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors (PARPi) to treat cancer relates to their ability to trap PARP-1 at the site of a DNA break. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. PMID:26626479 Poly(ADP-ribose)polymerase 1 (PARP-1) is a key eukaryotic stress sensor that responds in seconds to DNA single-strand breaks (SSBs), the most frequent genomic damage. |
| GO:0003684 damaged DNA binding | IDA PMID:32358582 Real-time monitoring of PARP1-dependent PARylation by ATR-FT... | ACCEPT | Summary: PARP1 zinc fingers recognise damaged DNA (single- and double-strand breaks and other lesions), which activates its catalytic domain. Reason: Damaged-DNA binding is the sensor half of PARP1 core function, demonstrated with purified protein and structural/biophysical studies of break recognition. Supporting Evidence: PMID:32358582 This includes PARP1 activation by binding to DNA strand break models, NAD+ substrate binding, PAR formation, and dissociation of automodified PARP1 from DNA. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. PMID:26626479 Poly(ADP-ribose)polymerase 1 (PARP-1) is a key eukaryotic stress sensor that responds in seconds to DNA single-strand breaks (SSBs), the most frequent genomic damage. |
| GO:0003684 damaged DNA binding | IDA PMID:37823600 ZNF432 stimulates PARylation and inhibits DNA resection to b... | ACCEPT | Summary: PARP1 zinc fingers recognise damaged DNA (single- and double-strand breaks and other lesions), which activates its catalytic domain. Reason: Damaged-DNA binding is the sensor half of PARP1 core function, demonstrated with purified protein and structural/biophysical studies of break recognition. Supporting Evidence: PMID:37823600 Remarkably, ZNF432 stimulates PARP-1 activity in vitro and in cellulo. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. PMID:26626479 Poly(ADP-ribose)polymerase 1 (PARP-1) is a key eukaryotic stress sensor that responds in seconds to DNA single-strand breaks (SSBs), the most frequent genomic damage. |
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | KEEP AS NON CORE | Summary: PARP1 was identified in high-throughput mRNA interactome capture screens. Reason: High-throughput RNA-interactome data support RNA association; PARP1 is known to bind some RNAs, but RNA binding is not a core function. Kept as non-core. Supporting Evidence: PMID:22658674 Employing two complementary protocols for covalent UV crosslinking of RBPs to RNA, we describe a systematic, unbiased, and comprehensive approach, termed "interactome capture," to define the mRNA interactome of proliferating human HeLa cells. |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | KEEP AS NON CORE | Summary: PARP1 was identified in high-throughput mRNA interactome capture screens. Reason: High-throughput RNA-interactome data support RNA association; PARP1 is known to bind some RNAs, but RNA binding is not a core function. Kept as non-core. Supporting Evidence: PMID:22681889 We developed a photoreactive nucleotide-enhanced UV crosslinking and oligo(dT) purification approach to identify the mRNA-bound proteome using quantitative proteomics and to display the protein occupancy on mRNA transcripts by next-generation sequencing. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | EXP PMID:18172500 Poly(ADP-ribose)-binding zinc finger motifs in DNA repair/ch... | ACCEPT | Summary: PARP1 is the founding DNA-dependent poly(ADP-ribose) polymerase: on binding DNA breaks it uses NAD+ to ADP-ribosylate itself and other acceptors and elongates ADP-ribose chains (EC 2.4.2.30); catalytic Glu988 is required for chain synthesis. Reason: This is the defining catalytic activity of PARP1 and is supported by abundant direct biochemical evidence (purified enzyme, catalytic-residue mutants, structural studies of DNA-dependent activation) and by the PAINT IBA. It is the core molecular function. Supporting Evidence: PMID:18172500 Poly(ADP-ribosyl)ation often involves the addition of long chains of ADP-ribose units, linked by glycosidic ribose-ribose bonds, and is critical for a wide range of processes, including DNA repair, regulation of chromosome structure, transcriptional regulation, mitosis and apoptosis. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:7852410 Glu988 of the human polymerase aligns with the catalytic glutamic acid of the toxins, and replacement of this residue with Gln, Asp, or Ala caused major reductions in synthesis of enzyme-linked poly-ADP-ribose. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | EXP PMID:25043379 Family-wide analysis of poly(ADP-ribose) polymerase activity... | ACCEPT | Summary: PARP1 is the founding DNA-dependent poly(ADP-ribose) polymerase: on binding DNA breaks it uses NAD+ to ADP-ribosylate itself and other acceptors and elongates ADP-ribose chains (EC 2.4.2.30); catalytic Glu988 is required for chain synthesis. Reason: This is the defining catalytic activity of PARP1 and is supported by abundant direct biochemical evidence (purified enzyme, catalytic-residue mutants, structural studies of DNA-dependent activation) and by the PAINT IBA. It is the core molecular function. Supporting Evidence: PMID:25043379 Here we show that the majority of PARPs generate MAR, not PAR, and demonstrate that the H-Y-E motif is not the sole indicator of PARP activity. PMID:25043379 We identify automodification sites on seven PARPs, and demonstrate that MAR and PAR generating PARPs modify similar amino acids, suggesting that the sequence and structural constraints limiting PARPs to MAR synthesis do not limit their ability to modify canonical amino-acid targets. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | EXP PMID:26344098 Timeless Interacts with PARP-1 to Promote Homologous Recombi... | ACCEPT | Summary: PARP1 is the founding DNA-dependent poly(ADP-ribose) polymerase: on binding DNA breaks it uses NAD+ to ADP-ribosylate itself and other acceptors and elongates ADP-ribose chains (EC 2.4.2.30); catalytic Glu988 is required for chain synthesis. Reason: This is the defining catalytic activity of PARP1 and is supported by abundant direct biochemical evidence (purified enzyme, catalytic-residue mutants, structural studies of DNA-dependent activation) and by the PAINT IBA. It is the core molecular function. Supporting Evidence: PMID:26344098 We demonstrate that rapid and transient accumulation of Timeless at laser-induced DNA damage sites requires PARP-1, but not poly(ADP-ribosyl)ation and that Timeless is co-trapped with PARP-1 at DNA lesions upon PARP inhibition. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:7852410 Glu988 of the human polymerase aligns with the catalytic glutamic acid of the toxins, and replacement of this residue with Gln, Asp, or Ala caused major reductions in synthesis of enzyme-linked poly-ADP-ribose. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PARP1 is the founding DNA-dependent poly(ADP-ribose) polymerase: on binding DNA breaks it uses NAD+ to ADP-ribosylate itself and other acceptors and elongates ADP-ribose chains (EC 2.4.2.30); catalytic Glu988 is required for chain synthesis. Reason: This is the defining catalytic activity of PARP1 and is supported by abundant direct biochemical evidence (purified enzyme, catalytic-residue mutants, structural studies of DNA-dependent activation) and by the PAINT IBA. It is the core molecular function. Supporting Evidence: PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:7852410 Glu988 of the human polymerase aligns with the catalytic glutamic acid of the toxins, and replacement of this residue with Gln, Asp, or Ala caused major reductions in synthesis of enzyme-linked poly-ADP-ribose. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IDA PMID:16107709 Cooperation of the Cockayne syndrome group B protein and pol... | ACCEPT | Summary: PARP1 is the founding DNA-dependent poly(ADP-ribose) polymerase: on binding DNA breaks it uses NAD+ to ADP-ribosylate itself and other acceptors and elongates ADP-ribose chains (EC 2.4.2.30); catalytic Glu988 is required for chain synthesis. Reason: This is the defining catalytic activity of PARP1 and is supported by abundant direct biochemical evidence (purified enzyme, catalytic-residue mutants, structural studies of DNA-dependent activation) and by the PAINT IBA. It is the core molecular function. Supporting Evidence: PMID:16107709 We find that CSB is present at sites of activated PARP-1 after oxidative stress, identify CSB as a new substrate of PARP-1, and demonstrate that poly(ADP-ribosyl)ation of CSB inhibits its DNA-dependent ATPase activity. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:7852410 Glu988 of the human polymerase aligns with the catalytic glutamic acid of the toxins, and replacement of this residue with Gln, Asp, or Ala caused major reductions in synthesis of enzyme-linked poly-ADP-ribose. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IDA PMID:17396150 A novel human AP endonuclease with conserved zinc-finger-lik... | ACCEPT | Summary: PARP1 is the founding DNA-dependent poly(ADP-ribose) polymerase: on binding DNA breaks it uses NAD+ to ADP-ribosylate itself and other acceptors and elongates ADP-ribose chains (EC 2.4.2.30); catalytic Glu988 is required for chain synthesis. Reason: This is the defining catalytic activity of PARP1 and is supported by abundant direct biochemical evidence (purified enzyme, catalytic-residue mutants, structural studies of DNA-dependent activation) and by the PAINT IBA. It is the core molecular function. Supporting Evidence: PMID:17396150 In mammalian cells, it has been shown in vitro and in vivo that SSBs activate poly(ADP-ribose) polymerases (PARP), which poly(ADP-ribosyl)ate proteins near SSBs as well as PARP itself. PMID:17396150 Indeed, PALF interacts directly with PARP1 and is required for its activation and for cellular resistance to methyl-methane sulfonate. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IDA PMID:18055453 A third zinc-binding domain of human poly(ADP-ribose) polyme... | ACCEPT | Summary: PARP1 is the founding DNA-dependent poly(ADP-ribose) polymerase: on binding DNA breaks it uses NAD+ to ADP-ribosylate itself and other acceptors and elongates ADP-ribose chains (EC 2.4.2.30); catalytic Glu988 is required for chain synthesis. Reason: This is the defining catalytic activity of PARP1 and is supported by abundant direct biochemical evidence (purified enzyme, catalytic-residue mutants, structural studies of DNA-dependent activation) and by the PAINT IBA. It is the core molecular function. Supporting Evidence: PMID:18055453 Here, we demonstrate using spectroscopic and crystallographic analysis that human PARP-1 has a third zinc-binding domain. PMID:18055453 Two zinc finger domains at the N terminus of PARP-1 bind to DNA and thereby activate the catalytic domain situated at the C terminus of the enzyme. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IDA PMID:19470756 SIRT1 promotes cell survival under stress by deacetylation-d... | ACCEPT | Summary: PARP1 is the founding DNA-dependent poly(ADP-ribose) polymerase: on binding DNA breaks it uses NAD+ to ADP-ribosylate itself and other acceptors and elongates ADP-ribose chains (EC 2.4.2.30); catalytic Glu988 is required for chain synthesis. Reason: This is the defining catalytic activity of PARP1 and is supported by abundant direct biochemical evidence (purified enzyme, catalytic-residue mutants, structural studies of DNA-dependent activation) and by the PAINT IBA. It is the core molecular function. Supporting Evidence: PMID:19470756 Here, we show that PARP1 is acetylated after stress of cardiomyocytes, resulting in the activation of PARP1, which is independent of DNA damage. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:7852410 Glu988 of the human polymerase aligns with the catalytic glutamic acid of the toxins, and replacement of this residue with Gln, Asp, or Ala caused major reductions in synthesis of enzyme-linked poly-ADP-ribose. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IDA PMID:19764761 Identification of the ADP-ribosylation sites in the PARP-1 a... | ACCEPT | Summary: PARP1 is the founding DNA-dependent poly(ADP-ribose) polymerase: on binding DNA breaks it uses NAD+ to ADP-ribosylate itself and other acceptors and elongates ADP-ribose chains (EC 2.4.2.30); catalytic Glu988 is required for chain synthesis. Reason: This is the defining catalytic activity of PARP1 and is supported by abundant direct biochemical evidence (purified enzyme, catalytic-residue mutants, structural studies of DNA-dependent activation) and by the PAINT IBA. It is the core molecular function. Supporting Evidence: PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:19764761 Here we report a strategy to identify the modification sites on domain D using the PARP-1 E988Q mutant, which only catalyzes mono(ADP-ribosyl)ation. PMID:7852410 Glu988 of the human polymerase aligns with the catalytic glutamic acid of the toxins, and replacement of this residue with Gln, Asp, or Ala caused major reductions in synthesis of enzyme-linked poly-ADP-ribose. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IDA PMID:20388712 The Zn3 domain of human poly(ADP-ribose) polymerase-1 (PARP-... | ACCEPT | Summary: PARP1 is the founding DNA-dependent poly(ADP-ribose) polymerase: on binding DNA breaks it uses NAD+ to ADP-ribosylate itself and other acceptors and elongates ADP-ribose chains (EC 2.4.2.30); catalytic Glu988 is required for chain synthesis. Reason: This is the defining catalytic activity of PARP1 and is supported by abundant direct biochemical evidence (purified enzyme, catalytic-residue mutants, structural studies of DNA-dependent activation) and by the PAINT IBA. It is the core molecular function. Supporting Evidence: PMID:20388712 PARP-1 attaches ADP-ribose units to target proteins, including itself as a post-translational modification that can change the biochemical properties of target proteins and mediate recruitment of proteins to sites of poly(ADP-ribose) synthesis. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:7852410 Glu988 of the human polymerase aligns with the catalytic glutamic acid of the toxins, and replacement of this residue with Gln, Asp, or Ala caused major reductions in synthesis of enzyme-linked poly-ADP-ribose. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IDA PMID:23275542 2,3,7,8-Tetrachlorodibenzo-p-dioxin poly(ADP-ribose) polymer... | ACCEPT | Summary: PARP1 is the founding DNA-dependent poly(ADP-ribose) polymerase: on binding DNA breaks it uses NAD+ to ADP-ribosylate itself and other acceptors and elongates ADP-ribose chains (EC 2.4.2.30); catalytic Glu988 is required for chain synthesis. Reason: This is the defining catalytic activity of PARP1 and is supported by abundant direct biochemical evidence (purified enzyme, catalytic-residue mutants, structural studies of DNA-dependent activation) and by the PAINT IBA. It is the core molecular function. Supporting Evidence: PMID:23275542 PARP-1 is activated by DNA strand breaks to modify target proteins with poly-ADP-ribose (2). PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:7852410 Glu988 of the human polymerase aligns with the catalytic glutamic acid of the toxins, and replacement of this residue with Gln, Asp, or Ala caused major reductions in synthesis of enzyme-linked poly-ADP-ribose. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IDA PMID:26626479 Structural Basis of Detection and Signaling of DNA Single-St... | ACCEPT | Summary: PARP1 is the founding DNA-dependent poly(ADP-ribose) polymerase: on binding DNA breaks it uses NAD+ to ADP-ribosylate itself and other acceptors and elongates ADP-ribose chains (EC 2.4.2.30); catalytic Glu988 is required for chain synthesis. Reason: This is the defining catalytic activity of PARP1 and is supported by abundant direct biochemical evidence (purified enzyme, catalytic-residue mutants, structural studies of DNA-dependent activation) and by the PAINT IBA. It is the core molecular function. Supporting Evidence: PMID:26626479 Poly(ADP-ribose)polymerase 1 (PARP-1) is a key eukaryotic stress sensor that responds in seconds to DNA single-strand breaks (SSBs), the most frequent genomic damage. PMID:26626479 Two flexibly linked N-terminal zinc fingers recognize the extreme deformability of SSBs and drive co-operative, stepwise self-assembly of remaining PARP-1 domains to control the activity of the C-terminal catalytic domain. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IDA PMID:26626480 PARP-1 Activation Requires Local Unfolding of an Autoinhibit... | ACCEPT | Summary: PARP1 is the founding DNA-dependent poly(ADP-ribose) polymerase: on binding DNA breaks it uses NAD+ to ADP-ribosylate itself and other acceptors and elongates ADP-ribose chains (EC 2.4.2.30); catalytic Glu988 is required for chain synthesis. Reason: This is the defining catalytic activity of PARP1 and is supported by abundant direct biochemical evidence (purified enzyme, catalytic-residue mutants, structural studies of DNA-dependent activation) and by the PAINT IBA. It is the core molecular function. Supporting Evidence: PMID:26626480 DNA breaks sharply elevate PARP-1 catalytic activity to mount a cell survival repair response, whereas persistent PARP-1 hyperactivation during severe genotoxic stress is associated with cell death. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:7852410 Glu988 of the human polymerase aligns with the catalytic glutamic acid of the toxins, and replacement of this residue with Gln, Asp, or Ala caused major reductions in synthesis of enzyme-linked poly-ADP-ribose. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IDA PMID:28190768 Serine ADP-Ribosylation Depends on HPF1. | ACCEPT | Summary: PARP1 is the founding DNA-dependent poly(ADP-ribose) polymerase: on binding DNA breaks it uses NAD+ to ADP-ribosylate itself and other acceptors and elongates ADP-ribose chains (EC 2.4.2.30); catalytic Glu988 is required for chain synthesis. Reason: This is the defining catalytic activity of PARP1 and is supported by abundant direct biochemical evidence (purified enzyme, catalytic-residue mutants, structural studies of DNA-dependent activation) and by the PAINT IBA. It is the core molecular function. Supporting Evidence: PMID:28190768 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. PMID:28190768 Moreover, adding HPF1 to in vitro PARP-1/PARP-2 reactions is necessary and sufficient for serine-specific ADPr of histones and PARP-1 itself. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IDA PMID:30104678 PARP2 mediates branched poly ADP-ribosylation in response to... | ACCEPT | Summary: PARP1 is the founding DNA-dependent poly(ADP-ribose) polymerase: on binding DNA breaks it uses NAD+ to ADP-ribosylate itself and other acceptors and elongates ADP-ribose chains (EC 2.4.2.30); catalytic Glu988 is required for chain synthesis. Reason: This is the defining catalytic activity of PARP1 and is supported by abundant direct biochemical evidence (purified enzyme, catalytic-residue mutants, structural studies of DNA-dependent activation) and by the PAINT IBA. It is the core molecular function. Supporting Evidence: PMID:30104678 Once DNA damage occurs, PARP1 is immediately recruited to the damaged DNA ends through its N-terminal DNA-binding motif, and stimulates PARylation via its C-terminal enzymatic domain20,21. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:7852410 Glu988 of the human polymerase aligns with the catalytic glutamic acid of the toxins, and replacement of this residue with Gln, Asp, or Ala caused major reductions in synthesis of enzyme-linked poly-ADP-ribose. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IDA PMID:32028527 HPF1 completes the PARP active site for DNA damage-induced A... | ACCEPT | Summary: PARP1 is the founding DNA-dependent poly(ADP-ribose) polymerase: on binding DNA breaks it uses NAD+ to ADP-ribosylate itself and other acceptors and elongates ADP-ribose chains (EC 2.4.2.30); catalytic Glu988 is required for chain synthesis. Reason: This is the defining catalytic activity of PARP1 and is supported by abundant direct biochemical evidence (purified enzyme, catalytic-residue mutants, structural studies of DNA-dependent activation) and by the PAINT IBA. It is the core molecular function. Supporting Evidence: PMID:32028527 After binding to genomic lesions, these enzymes use NAD+ to modify numerous proteins with mono- and poly(ADP-ribose) signals that are important for the subsequent decompaction of chromatin and the recruitment of repair factors3,4. PMID:32028527 These post-translational modifications are predominantly serine-linked and require the accessory factor HPF1, which is specific for the DNA damage response and switches the amino acid specificity of PARP1 and PARP2 from aspartate or glutamate to serine residues5-10. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IDA PMID:32241924 Structural basis for allosteric PARP-1 retention on DNA brea... | ACCEPT | Summary: PARP1 is the founding DNA-dependent poly(ADP-ribose) polymerase: on binding DNA breaks it uses NAD+ to ADP-ribosylate itself and other acceptors and elongates ADP-ribose chains (EC 2.4.2.30); catalytic Glu988 is required for chain synthesis. Reason: This is the defining catalytic activity of PARP1 and is supported by abundant direct biochemical evidence (purified enzyme, catalytic-residue mutants, structural studies of DNA-dependent activation) and by the PAINT IBA. It is the core molecular function. Supporting Evidence: PMID:32241924 The success of poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors (PARPi) to treat cancer relates to their ability to trap PARP-1 at the site of a DNA break. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:7852410 Glu988 of the human polymerase aligns with the catalytic glutamic acid of the toxins, and replacement of this residue with Gln, Asp, or Ala caused major reductions in synthesis of enzyme-linked poly-ADP-ribose. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IDA PMID:32358582 Real-time monitoring of PARP1-dependent PARylation by ATR-FT... | ACCEPT | Summary: PARP1 is the founding DNA-dependent poly(ADP-ribose) polymerase: on binding DNA breaks it uses NAD+ to ADP-ribosylate itself and other acceptors and elongates ADP-ribose chains (EC 2.4.2.30); catalytic Glu988 is required for chain synthesis. Reason: This is the defining catalytic activity of PARP1 and is supported by abundant direct biochemical evidence (purified enzyme, catalytic-residue mutants, structural studies of DNA-dependent activation) and by the PAINT IBA. It is the core molecular function. Supporting Evidence: PMID:32358582 This includes PARP1 activation by binding to DNA strand break models, NAD+ substrate binding, PAR formation, and dissociation of automodified PARP1 from DNA. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:7852410 Glu988 of the human polymerase aligns with the catalytic glutamic acid of the toxins, and replacement of this residue with Gln, Asp, or Ala caused major reductions in synthesis of enzyme-linked poly-ADP-ribose. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IDA PMID:33186521 An HPF1/PARP1-Based Chemical Biology Strategy for Exploring ... | ACCEPT | Summary: PARP1 is the founding DNA-dependent poly(ADP-ribose) polymerase: on binding DNA breaks it uses NAD+ to ADP-ribosylate itself and other acceptors and elongates ADP-ribose chains (EC 2.4.2.30); catalytic Glu988 is required for chain synthesis. Reason: This is the defining catalytic activity of PARP1 and is supported by abundant direct biochemical evidence (purified enzyme, catalytic-residue mutants, structural studies of DNA-dependent activation) and by the PAINT IBA. It is the core molecular function. Supporting Evidence: PMID:33186521 An HPF1/PARP1-Based Chemical Biology Strategy for Exploring ADP-Ribosylation. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:7852410 Glu988 of the human polymerase aligns with the catalytic glutamic acid of the toxins, and replacement of this residue with Gln, Asp, or Ala caused major reductions in synthesis of enzyme-linked poly-ADP-ribose. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IDA PMID:33683197 HPF1 and nucleosomes mediate a dramatic switch in activity o... | ACCEPT | Summary: PARP1 is the founding DNA-dependent poly(ADP-ribose) polymerase: on binding DNA breaks it uses NAD+ to ADP-ribosylate itself and other acceptors and elongates ADP-ribose chains (EC 2.4.2.30); catalytic Glu988 is required for chain synthesis. Reason: This is the defining catalytic activity of PARP1 and is supported by abundant direct biochemical evidence (purified enzyme, catalytic-residue mutants, structural studies of DNA-dependent activation) and by the PAINT IBA. It is the core molecular function. Supporting Evidence: PMID:33683197 HPF1 provides that catalytic base Glu284 to substantially redirect PARylation by PARP1 such that the histones in nucleosomes become the primary recipients of PAR chains. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:7852410 Glu988 of the human polymerase aligns with the catalytic glutamic acid of the toxins, and replacement of this residue with Gln, Asp, or Ala caused major reductions in synthesis of enzyme-linked poly-ADP-ribose. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IDA PMID:34732825 Dual function of HPF1 in the modulation of PARP1 and PARP2 a... | ACCEPT | Summary: PARP1 is the founding DNA-dependent poly(ADP-ribose) polymerase: on binding DNA breaks it uses NAD+ to ADP-ribosylate itself and other acceptors and elongates ADP-ribose chains (EC 2.4.2.30); catalytic Glu988 is required for chain synthesis. Reason: This is the defining catalytic activity of PARP1 and is supported by abundant direct biochemical evidence (purified enzyme, catalytic-residue mutants, structural studies of DNA-dependent activation) and by the PAINT IBA. It is the core molecular function. Supporting Evidence: PMID:34732825 Here we demonstrate that HPF1 can stimulate the DNA-dependent and DNA-independent autoPARylation of PARP1 and PARP2 as well as the heteroPARylation of histones in the complex with nucleosome. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:7852410 Glu988 of the human polymerase aligns with the catalytic glutamic acid of the toxins, and replacement of this residue with Gln, Asp, or Ala caused major reductions in synthesis of enzyme-linked poly-ADP-ribose. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IDA PMID:34795260 HPF1 dynamically controls the PARP1/2 balance between initia... | ACCEPT | Summary: PARP1 is the founding DNA-dependent poly(ADP-ribose) polymerase: on binding DNA breaks it uses NAD+ to ADP-ribosylate itself and other acceptors and elongates ADP-ribose chains (EC 2.4.2.30); catalytic Glu988 is required for chain synthesis. Reason: This is the defining catalytic activity of PARP1 and is supported by abundant direct biochemical evidence (purified enzyme, catalytic-residue mutants, structural studies of DNA-dependent activation) and by the PAINT IBA. It is the core molecular function. Supporting Evidence: PMID:34795260 HPF1 rapidly associates/dissociates from multiple PARP1 molecules, initiating serine modification before modification initiates on glutamate/aspartate, and accelerating initiation to be more comparable to elongation reactions forming poly(ADP-ribose). PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:7852410 Glu988 of the human polymerase aligns with the catalytic glutamic acid of the toxins, and replacement of this residue with Gln, Asp, or Ala caused major reductions in synthesis of enzyme-linked poly-ADP-ribose. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IDA PMID:35219381 Micropeptide PACMP inhibition elicits synthetic lethal effec... | ACCEPT | Summary: PARP1 is the founding DNA-dependent poly(ADP-ribose) polymerase: on binding DNA breaks it uses NAD+ to ADP-ribosylate itself and other acceptors and elongates ADP-ribose chains (EC 2.4.2.30); catalytic Glu988 is required for chain synthesis. Reason: This is the defining catalytic activity of PARP1 and is supported by abundant direct biochemical evidence (purified enzyme, catalytic-residue mutants, structural studies of DNA-dependent activation) and by the PAINT IBA. It is the core molecular function. Supporting Evidence: PMID:35219381 PACMP not only prevents CtIP from ubiquitination through inhibiting the CtIP-KLHL15 association but also directly binds DNA damage-induced poly(ADP-ribose) chains to enhance PARP1-dependent poly(ADP-ribosyl)ation. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:7852410 Glu988 of the human polymerase aligns with the catalytic glutamic acid of the toxins, and replacement of this residue with Gln, Asp, or Ala caused major reductions in synthesis of enzyme-linked poly-ADP-ribose. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IDA PMID:7852410 Role of glutamic acid 988 of human poly-ADP-ribose polymeras... | ACCEPT | Summary: PARP1 is the founding DNA-dependent poly(ADP-ribose) polymerase: on binding DNA breaks it uses NAD+ to ADP-ribosylate itself and other acceptors and elongates ADP-ribose chains (EC 2.4.2.30); catalytic Glu988 is required for chain synthesis. Reason: This is the defining catalytic activity of PARP1 and is supported by abundant direct biochemical evidence (purified enzyme, catalytic-residue mutants, structural studies of DNA-dependent activation) and by the PAINT IBA. It is the core molecular function. Supporting Evidence: PMID:7852410 Glu988 of the human polymerase aligns with the catalytic glutamic acid of the toxins, and replacement of this residue with Gln, Asp, or Ala caused major reductions in synthesis of enzyme-linked poly-ADP-ribose. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: PARP1 is the founding DNA-dependent poly(ADP-ribose) polymerase: on binding DNA breaks it uses NAD+ to ADP-ribosylate itself and other acceptors and elongates ADP-ribose chains (EC 2.4.2.30); catalytic Glu988 is required for chain synthesis. Reason: This is the defining catalytic activity of PARP1 and is supported by abundant direct biochemical evidence (purified enzyme, catalytic-residue mutants, structural studies of DNA-dependent activation) and by the PAINT IBA. It is the core molecular function. Supporting Evidence: PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:7852410 Glu988 of the human polymerase aligns with the catalytic glutamic acid of the toxins, and replacement of this residue with Gln, Asp, or Ala caused major reductions in synthesis of enzyme-linked poly-ADP-ribose. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IMP PMID:22504299 Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-Ξ³... | ACCEPT | Summary: PARP1 is the founding DNA-dependent poly(ADP-ribose) polymerase: on binding DNA breaks it uses NAD+ to ADP-ribosylate itself and other acceptors and elongates ADP-ribose chains (EC 2.4.2.30); catalytic Glu988 is required for chain synthesis. Reason: This is the defining catalytic activity of PARP1 and is supported by abundant direct biochemical evidence (purified enzyme, catalytic-residue mutants, structural studies of DNA-dependent activation) and by the PAINT IBA. It is the core molecular function. Supporting Evidence: PMID:22504299 Here we report a nuclear complex of TrpRS with the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) and with poly(ADP-ribose) polymerase 1 (PARP-1), the major PARP in human cells. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:7852410 Glu988 of the human polymerase aligns with the catalytic glutamic acid of the toxins, and replacement of this residue with Gln, Asp, or Ala caused major reductions in synthesis of enzyme-linked poly-ADP-ribose. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | TAS PMID:2513174 Human nuclear NAD+ ADP-ribosyltransferase(polymerizing): org... | ACCEPT | Summary: PARP1 is the founding DNA-dependent poly(ADP-ribose) polymerase: on binding DNA breaks it uses NAD+ to ADP-ribosylate itself and other acceptors and elongates ADP-ribose chains (EC 2.4.2.30); catalytic Glu988 is required for chain synthesis. Reason: This is the defining catalytic activity of PARP1 and is supported by abundant direct biochemical evidence (purified enzyme, catalytic-residue mutants, structural studies of DNA-dependent activation) and by the PAINT IBA. It is the core molecular function. Supporting Evidence: PMID:2513174 Each of the four metal coordinating sites putatively forming the two zinc fingers of the DNA-binding domain is encoded separately. PMID:2513174 The automodification domain and the NAD-binding domain are coded for by 4 and 12 exons, respectively. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | TAS Reactome:R-HSA-2187325 | ACCEPT | Summary: PARP1 is the founding DNA-dependent poly(ADP-ribose) polymerase: on binding DNA breaks it uses NAD+ to ADP-ribosylate itself and other acceptors and elongates ADP-ribose chains (EC 2.4.2.30); catalytic Glu988 is required for chain synthesis. Reason: This is the defining catalytic activity of PARP1 and is supported by abundant direct biochemical evidence (purified enzyme, catalytic-residue mutants, structural studies of DNA-dependent activation) and by the PAINT IBA. It is the core molecular function. Supporting Evidence: PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:7852410 Glu988 of the human polymerase aligns with the catalytic glutamic acid of the toxins, and replacement of this residue with Gln, Asp, or Ala caused major reductions in synthesis of enzyme-linked poly-ADP-ribose. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005515 protein binding | IPI PMID:11248244 Characterization of recombinant human nicotinamide mononucle... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:14596914 Physical and functional interaction of the Werner syndrome p... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:14627987 PARP-1 binds E2F-1 independently of its DNA binding and cata... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:14627987 PARP-1 binds E2F-1 independently of its DNA binding and cata... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:14734561 Identification and biochemical characterization of a Werner'... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:15044383 Aprataxin, a novel protein that protects against genotoxic s... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:15044383 Aprataxin, a novel protein that protects against genotoxic s... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:15044383 Aprataxin, a novel protein that protects against genotoxic s... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:15555565 The FHA domain of aprataxin interacts with the C-terminal re... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:16107709 Cooperation of the Cockayne syndrome group B protein and pol... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:16490787 In prostate cancer cells the interaction of C/EBPalpha with ... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:17167422 Hsp70 regulates erythropoiesis by preventing caspase-3-media... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:17396150 A novel human AP endonuclease with conserved zinc-finger-lik... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:18172500 Poly(ADP-ribose)-binding zinc finger motifs in DNA repair/ch... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:18172500 Poly(ADP-ribose)-binding zinc finger motifs in DNA repair/ch... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:18971944 Chk2-dependent phosphorylation of XRCC1 in the DNA damage re... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:19661379 Poly(ADP-ribose)-dependent regulation of DNA repair by the c... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:19661379 Poly(ADP-ribose)-dependent regulation of DNA repair by the c... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:19666485 Poly(ADP-ribosyl)ation directs recruitment and activation of... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:19710015 The metastasis efficiency modifier ribosomal RNA processing ... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:19779455 PARP-1 transcriptional activity is regulated by sumoylation ... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:19779455 PARP-1 transcriptional activity is regulated by sumoylation ... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:19779455 PARP-1 transcriptional activity is regulated by sumoylation ... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:20064938 PARP-3 is a mono-ADP-ribosylase that activates PARP-1 in the... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:20098424 Solution structures of the two PBZ domains from human APLF a... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:20133863 Inhibition of poly(ADP-ribose) polymerase down-regulates BRC... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:21266351 hPuf-A/KIAA0020 modulates PARP-1 cleavage upon genotoxic str... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:21549307 Maintenance of silent chromatin through replication requires... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:21575865 Mechanistic rationale for inhibition of poly(ADP-ribose) pol... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:21577210 Poly(ADP-ribose)-dependent regulation of Snail1 protein stab... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:21577210 Poly(ADP-ribose)-dependent regulation of Snail1 protein stab... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:21799911 Ubiquitin ligase RNF146 regulates tankyrase and Axin to prom... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:22504299 Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-Ξ³... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:22504299 Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-Ξ³... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:22504299 Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-Ξ³... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:22504299 Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-Ξ³... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:22863007 Exome capture reveals ZNF423 and CEP164 mutations, linking r... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:23213405 Taperin (c9orf75), a mutated gene in nonsyndromic deafness, ... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:23230272 BAL1 and its partner E3 ligase, BBAP, link Poly(ADP-ribose) ... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:23396353 Human RECQ1 promotes restart of replication forks reversed b... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:23481255 Deficiency of terminal ADP-ribose protein glycohydrolase TAR... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:23966166 ZNF365 promotes stalled replication forks recovery to mainta... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:24145797 PARP1 orchestrates variant histone exchange in signal-mediat... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:24145797 PARP1 orchestrates variant histone exchange in signal-mediat... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:24778456 S-sulfhydration of MEK1 leads to PARP-1 activation and DNA d... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:25533949 A human tRNA synthetase is a potent PARP1-activating effecto... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:25640309 Systematic identification of molecular links between core an... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:25749521 TNKS1BP1 functions in DNA double-strand break repair though ... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:25749521 TNKS1BP1 functions in DNA double-strand break repair though ... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:25749521 TNKS1BP1 functions in DNA double-strand break repair though ... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:26344098 Timeless Interacts with PARP-1 to Promote Homologous Recombi... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:27067600 HPF1/C4orf27 Is a PARP-1-Interacting Protein that Regulates ... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:27248496 WDR76 Co-Localizes with Heterochromatin Related Proteins and... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:27728808 Enhancing the Cytotoxic Effects of PARP Inhibitors with DNA ... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:28190768 Serine ADP-Ribosylation Depends on HPF1. | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:29721183 Delineating the HMGB1 and HMGB2 interactome in prostate and ... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:30356214 Nuclear cGAS suppresses DNA repair and promotes tumorigenesi... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:30356214 Nuclear cGAS suppresses DNA repair and promotes tumorigenesi... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:30356214 Nuclear cGAS suppresses DNA repair and promotes tumorigenesi... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:31609975 KHDC3L mutation causes recurrent pregnancy loss by inducing ... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:31796734 Barrier-to-autointegration factor 1 (Banf1) regulates poly [... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:33412112 CARM1 regulates replication fork speed and stress response b... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:34102106 XRCC1 prevents toxic PARP1 trapping during DNA base excision... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:35025765 RECON syndrome is a genome instability disorder caused by mu... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:35219381 Micropeptide PACMP inhibition elicits synthetic lethal effec... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:37207277 Using brain cell-type-specific protein interactomes to inter... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:38884001 Mapping adipocyte interactome networks by HaloTag-enrichment... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:7596430 Identification and inhibition of the ICE/CED-3 protease nece... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:9518481 Functional association of poly(ADP-ribose) polymerase with D... | REMOVE | Summary: Generic protein binding annotation from interaction studies. Reason: Protein binding (GO:0005515) is uninformative about PARP1 function. Removal does not dispute the reported interaction; informative functions (ADP-ribosyltransferase activity, damaged DNA binding, nucleosome binding) are captured by other annotations. |
| GO:0005634 nucleus | EXP PMID:21799911 Ubiquitin ligase RNF146 regulates tankyrase and Axin to prom... | ACCEPT | Summary: PARP1 is a nuclear protein with an N-terminal bipartite NLS. Reason: Nuclear localization is well established and is where PARP1 performs its core DNA damage functions. Supporting Evidence: PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). |
| GO:0005634 nucleus | EXP PMID:23230272 BAL1 and its partner E3 ligase, BBAP, link Poly(ADP-ribose) ... | ACCEPT | Summary: PARP1 is a nuclear protein with an N-terminal bipartite NLS. Reason: Nuclear localization is well established and is where PARP1 performs its core DNA damage functions. Supporting Evidence: PMID:23230272 These data establish that BAL1 and BBAP are bona fide members of a DNA damage response pathway and are directly associated with PARP1 activation, BRCA1 recruitment, and double-strand break repair. PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). |
| GO:0005634 nucleus | IDA PMID:17177976 Txk, a member of the non-receptor tyrosine kinase of the Tec... | ACCEPT | Summary: PARP1 is a nuclear protein with an N-terminal bipartite NLS. Reason: Nuclear localization is well established and is where PARP1 performs its core DNA damage functions. Supporting Evidence: PMID:17177976 Upon activation, a complex involving Txk, EF-1alpha and PARP1 was formed and was located in the nucleus. PMID:17177976 Txk phosphorylated EF-1alpha and PARP1 formed a complex with them, and bound to the IFN-gamma gene promoter in vitro. PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). |
| GO:0005634 nucleus | IDA PMID:22464733 Inflammasome-activated caspase 7 cleaves PARP1 to enhance th... | ACCEPT | Summary: PARP1 is a nuclear protein with an N-terminal bipartite NLS. Reason: Nuclear localization is well established and is where PARP1 performs its core DNA damage functions. Supporting Evidence: PMID:22464733 Here we show that after LPS stimulation, caspase 7 is activated by caspase 1, translocates to the nucleus, and cleaves PARP1 at the promoters of a subset of NF-ΞΊB target genes negatively regulated by PARP1. PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). |
| GO:0005634 nucleus | IDA PMID:22504299 Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-Ξ³... | ACCEPT | Summary: PARP1 is a nuclear protein with an N-terminal bipartite NLS. Reason: Nuclear localization is well established and is where PARP1 performs its core DNA damage functions. Supporting Evidence: PMID:22504299 Here we report a nuclear complex of TrpRS with the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) and with poly(ADP-ribose) polymerase 1 (PARP-1), the major PARP in human cells. PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). |
| GO:0005634 nucleus | IDA PMID:27256882 Chemical genetic discovery of PARP targets reveals a role fo... | ACCEPT | Summary: PARP1 is a nuclear protein with an N-terminal bipartite NLS. Reason: Nuclear localization is well established and is where PARP1 performs its core DNA damage functions. Supporting Evidence: PMID:27256882 We found that PARP-1 ADP-ribosylates and inhibits negative elongation factor (NELF), a protein complex that regulates promoter-proximal pausing by RNA polymerase II (Pol II). PMID:27256882 Using this approach, we mapped hundreds of sites of ADP-ribosylation for PARPs 1, 2, and 3 across the proteome, as well as thousands of PARP-1-mediated ADP-ribosylation sites across the genome. PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). |
| GO:0005634 nucleus | IDA PMID:34102106 XRCC1 prevents toxic PARP1 trapping during DNA base excision... | ACCEPT | Summary: PARP1 is a nuclear protein with an N-terminal bipartite NLS. Reason: Nuclear localization is well established and is where PARP1 performs its core DNA damage functions. Supporting Evidence: PMID:34102106 PARPs are sensors that detect single-strand break intermediates, but the critical role of XRCC1 during BER is unknown. PMID:34102106 Consequently, PARP1 deletion rescues BER and resistance to base damage in XRCC1-/- cells. PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). |
| GO:0005634 nucleus | IDA PMID:35393539 Poly(ADP-ribosylation) of P-TEFb by PARP1 disrupts phase sep... | ACCEPT | Summary: PARP1 is a nuclear protein with an N-terminal bipartite NLS. Reason: Nuclear localization is well established and is where PARP1 performs its core DNA damage functions. Supporting Evidence: PMID:35393539 Here we report that PARP1 inhibits Pol II elongation by inactivating the transcription elongation factor P-TEFb, a CDK9-cyclin T1 (CycT1) heterodimer. PMID:35393539 After sensing damage, the activated PARP1 binds to transcriptionally engaged P-TEFb and modifies CycT1 at multiple positions, including histidine residues that are rarely used as an acceptor site. PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). |
| GO:0005634 nucleus | IDA PMID:35460603 Cytoplasmic PARP1 links the genome instability to the inhibi... | ACCEPT | Summary: PARP1 is a nuclear protein with an N-terminal bipartite NLS. Reason: Nuclear localization is well established and is where PARP1 performs its core DNA damage functions. Supporting Evidence: PMID:35460603 Activated DNA-PK phosphorylates PARP1 on Thr594, thus facilitating the cytoplasmic translocation of PARP1 to inhibit the antiviral immunity both in vitro and in vivo. PMID:35460603 Mechanistically, cytoplasmic PARP1 interacts with and directly PARylates cyclic GMP-AMP synthase (cGAS) on Asp191 to inhibit its DNA-binding ability. PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). |
| GO:0005634 nucleus | IDA PMID:37823600 ZNF432 stimulates PARylation and inhibits DNA resection to b... | ACCEPT | Summary: PARP1 is a nuclear protein with an N-terminal bipartite NLS. Reason: Nuclear localization is well established and is where PARP1 performs its core DNA damage functions. Supporting Evidence: PMID:37823600 Remarkably, ZNF432 stimulates PARP-1 activity in vitro and in cellulo. PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: PARP1 is a nuclear protein with an N-terminal bipartite NLS. Reason: Nuclear localization is well established and is where PARP1 performs its core DNA damage functions. Supporting Evidence: PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). |
| GO:0005634 nucleus | TAS PMID:2513174 Human nuclear NAD+ ADP-ribosyltransferase(polymerizing): org... | ACCEPT | Summary: PARP1 is a nuclear protein with an N-terminal bipartite NLS. Reason: Nuclear localization is well established and is where PARP1 performs its core DNA damage functions. Supporting Evidence: PMID:2513174 Each of the four metal coordinating sites putatively forming the two zinc fingers of the DNA-binding domain is encoded separately. PMID:2513174 The automodification domain and the NAD-binding domain are coded for by 4 and 12 exons, respectively. PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). |
| GO:0005635 nuclear envelope | IDA PMID:9518481 Functional association of poly(ADP-ribose) polymerase with D... | KEEP AS NON CORE | Summary: PARP was observed at the nuclear envelope/periphery in a localization study. Reason: Experimental observation, minor localization; non-core. Supporting Evidence: PMID:9518481 Altogether, the present results strongly suggest that PARP participates in a DNA damage survey mechanism implying its nick-sensor function as part of the control of replication fork progression when breaks are present in the template. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: PARP1 is located in the nucleoplasm, where it binds chromatin and DNA lesions. Reason: Consistent with nuclear localization and Reactome DNA repair reactions; accepted. Supporting Evidence: PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2187325 | ACCEPT | Summary: PARP1 is located in the nucleoplasm, where it binds chromatin and DNA lesions. Reason: Consistent with nuclear localization and Reactome DNA repair reactions; accepted. Supporting Evidence: PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2187330 | ACCEPT | Summary: PARP1 is located in the nucleoplasm, where it binds chromatin and DNA lesions. Reason: Consistent with nuclear localization and Reactome DNA repair reactions; accepted. Supporting Evidence: PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-4551604 | ACCEPT | Summary: PARP1 is located in the nucleoplasm, where it binds chromatin and DNA lesions. Reason: Consistent with nuclear localization and Reactome DNA repair reactions; accepted. Supporting Evidence: PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-4551768 | ACCEPT | Summary: PARP1 is located in the nucleoplasm, where it binds chromatin and DNA lesions. Reason: Consistent with nuclear localization and Reactome DNA repair reactions; accepted. Supporting Evidence: PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5649873 | ACCEPT | Summary: PARP1 is located in the nucleoplasm, where it binds chromatin and DNA lesions. Reason: Consistent with nuclear localization and Reactome DNA repair reactions; accepted. Supporting Evidence: PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5649883 | ACCEPT | Summary: PARP1 is located in the nucleoplasm, where it binds chromatin and DNA lesions. Reason: Consistent with nuclear localization and Reactome DNA repair reactions; accepted. Supporting Evidence: PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5651723 | ACCEPT | Summary: PARP1 is located in the nucleoplasm, where it binds chromatin and DNA lesions. Reason: Consistent with nuclear localization and Reactome DNA repair reactions; accepted. Supporting Evidence: PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5651739 | ACCEPT | Summary: PARP1 is located in the nucleoplasm, where it binds chromatin and DNA lesions. Reason: Consistent with nuclear localization and Reactome DNA repair reactions; accepted. Supporting Evidence: PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5651828 | ACCEPT | Summary: PARP1 is located in the nucleoplasm, where it binds chromatin and DNA lesions. Reason: Consistent with nuclear localization and Reactome DNA repair reactions; accepted. Supporting Evidence: PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5687484 | ACCEPT | Summary: PARP1 is located in the nucleoplasm, where it binds chromatin and DNA lesions. Reason: Consistent with nuclear localization and Reactome DNA repair reactions; accepted. Supporting Evidence: PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5687640 | ACCEPT | Summary: PARP1 is located in the nucleoplasm, where it binds chromatin and DNA lesions. Reason: Consistent with nuclear localization and Reactome DNA repair reactions; accepted. Supporting Evidence: PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5687653 | ACCEPT | Summary: PARP1 is located in the nucleoplasm, where it binds chromatin and DNA lesions. Reason: Consistent with nuclear localization and Reactome DNA repair reactions; accepted. Supporting Evidence: PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5689317 | ACCEPT | Summary: PARP1 is located in the nucleoplasm, where it binds chromatin and DNA lesions. Reason: Consistent with nuclear localization and Reactome DNA repair reactions; accepted. Supporting Evidence: PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5689861 | ACCEPT | Summary: PARP1 is located in the nucleoplasm, where it binds chromatin and DNA lesions. Reason: Consistent with nuclear localization and Reactome DNA repair reactions; accepted. Supporting Evidence: PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5690213 | ACCEPT | Summary: PARP1 is located in the nucleoplasm, where it binds chromatin and DNA lesions. Reason: Consistent with nuclear localization and Reactome DNA repair reactions; accepted. Supporting Evidence: PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5690988 | ACCEPT | Summary: PARP1 is located in the nucleoplasm, where it binds chromatin and DNA lesions. Reason: Consistent with nuclear localization and Reactome DNA repair reactions; accepted. Supporting Evidence: PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5690990 | ACCEPT | Summary: PARP1 is located in the nucleoplasm, where it binds chromatin and DNA lesions. Reason: Consistent with nuclear localization and Reactome DNA repair reactions; accepted. Supporting Evidence: PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5690991 | ACCEPT | Summary: PARP1 is located in the nucleoplasm, where it binds chromatin and DNA lesions. Reason: Consistent with nuclear localization and Reactome DNA repair reactions; accepted. Supporting Evidence: PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5690996 | ACCEPT | Summary: PARP1 is located in the nucleoplasm, where it binds chromatin and DNA lesions. Reason: Consistent with nuclear localization and Reactome DNA repair reactions; accepted. Supporting Evidence: PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5691000 | ACCEPT | Summary: PARP1 is located in the nucleoplasm, where it binds chromatin and DNA lesions. Reason: Consistent with nuclear localization and Reactome DNA repair reactions; accepted. Supporting Evidence: PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5696655 | ACCEPT | Summary: PARP1 is located in the nucleoplasm, where it binds chromatin and DNA lesions. Reason: Consistent with nuclear localization and Reactome DNA repair reactions; accepted. Supporting Evidence: PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5696664 | ACCEPT | Summary: PARP1 is located in the nucleoplasm, where it binds chromatin and DNA lesions. Reason: Consistent with nuclear localization and Reactome DNA repair reactions; accepted. Supporting Evidence: PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5696670 | ACCEPT | Summary: PARP1 is located in the nucleoplasm, where it binds chromatin and DNA lesions. Reason: Consistent with nuclear localization and Reactome DNA repair reactions; accepted. Supporting Evidence: PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6790454 | ACCEPT | Summary: PARP1 is located in the nucleoplasm, where it binds chromatin and DNA lesions. Reason: Consistent with nuclear localization and Reactome DNA repair reactions; accepted. Supporting Evidence: PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6790487 | ACCEPT | Summary: PARP1 is located in the nucleoplasm, where it binds chromatin and DNA lesions. Reason: Consistent with nuclear localization and Reactome DNA repair reactions; accepted. Supporting Evidence: PMID:21799911 In contrast to tankyrase, PARP1 shows exclusively nuclear localization that is not altered by XAV939 treatment (Figure S4). PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005667 transcription regulator complex | IDA PMID:19303849 A role of DNA-PK for the metabolic gene regulation in respon... | KEEP AS NON CORE | Summary: PARP1 is present in a transcription regulator complex at the FAS promoter. Reason: Context-specific; non-core. Supporting Evidence: PMID:19303849 Upon feeding, HDAC9 was no longer bound to the promoter, but the FAS promoter was now occupied by the coactivator P/CAF, DNA break/repair components that include DNA-PK, Ku70/80, PARP-1, TopoIIΞ², as well as PP1 (Fig. 1C, left panel). |
| GO:0005694 chromosome | EXP PMID:15607977 NAD+-dependent modulation of chromatin structure and transcr... | ACCEPT | Summary: PARP1 associates with chromosomes/chromatin and is recruited to damaged DNA. Reason: Well supported by chromatin binding and recruitment studies; accepted. Supporting Evidence: PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. PMID:15607977 Herein, we describe previously uncharacterized nucleosome binding properties of PARP-1 that promote the formation of compact, transcriptionally repressed chromatin structures. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005694 chromosome | EXP PMID:22683995 The zinc-finger domains of PARP1 cooperate to recognize DNA ... | ACCEPT | Summary: PARP1 associates with chromosomes/chromatin and is recruited to damaged DNA. Reason: Well supported by chromatin binding and recruitment studies; accepted. Supporting Evidence: PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. PMID:22683995 Upon activation at sites of DNA damage, PARP1 modifies itself and other proteins by covalent addition of long, branched polymers of ADP-ribose, which in turn recruit downstream DNA repair and chromatin remodeling factors. PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. |
| GO:0005694 chromosome | EXP PMID:23230272 BAL1 and its partner E3 ligase, BBAP, link Poly(ADP-ribose) ... | ACCEPT | Summary: PARP1 associates with chromosomes/chromatin and is recruited to damaged DNA. Reason: Well supported by chromatin binding and recruitment studies; accepted. Supporting Evidence: PMID:23230272 These data establish that BAL1 and BBAP are bona fide members of a DNA damage response pathway and are directly associated with PARP1 activation, BRCA1 recruitment, and double-strand break repair. PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005694 chromosome | EXP PMID:26344098 Timeless Interacts with PARP-1 to Promote Homologous Recombi... | ACCEPT | Summary: PARP1 associates with chromosomes/chromatin and is recruited to damaged DNA. Reason: Well supported by chromatin binding and recruitment studies; accepted. Supporting Evidence: PMID:26344098 We demonstrate that rapid and transient accumulation of Timeless at laser-induced DNA damage sites requires PARP-1, but not poly(ADP-ribosyl)ation and that Timeless is co-trapped with PARP-1 at DNA lesions upon PARP inhibition. PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005694 chromosome | EXP PMID:27568560 JNK Phosphorylates SIRT6 to Stimulate DNA Double-Strand Brea... | ACCEPT | Summary: PARP1 associates with chromosomes/chromatin and is recruited to damaged DNA. Reason: Well supported by chromatin binding and recruitment studies; accepted. Supporting Evidence: PMID:27568560 This post-translational modification facilitates the mobilization of SIRT6 to DNA damage sites and is required for efficient recruitment of poly (ADP-ribose) polymerase 1 (PARP1) to DNA break sites and for efficient repair of DSBs. PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005694 chromosome | EXP PMID:30675909 Increased PARP1-DNA binding due to autoPARylation inhibition... | ACCEPT | Summary: PARP1 associates with chromosomes/chromatin and is recruited to damaged DNA. Reason: Well supported by chromatin binding and recruitment studies; accepted. Supporting Evidence: PMID:30675909 PARP1 inhibitors (PARPis) are used clinically during cancer therapy and are thought to exert their cytotoxicity through PARP1 polymerase inhibition and PARP1-DNA trapping. PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005694 chromosome | EXP PMID:32241924 Structural basis for allosteric PARP-1 retention on DNA brea... | ACCEPT | Summary: PARP1 associates with chromosomes/chromatin and is recruited to damaged DNA. Reason: Well supported by chromatin binding and recruitment studies; accepted. Supporting Evidence: PMID:32241924 The success of poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors (PARPi) to treat cancer relates to their ability to trap PARP-1 at the site of a DNA break. PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005694 chromosome | EXP PMID:32358582 Real-time monitoring of PARP1-dependent PARylation by ATR-FT... | ACCEPT | Summary: PARP1 associates with chromosomes/chromatin and is recruited to damaged DNA. Reason: Well supported by chromatin binding and recruitment studies; accepted. Supporting Evidence: PMID:32358582 This includes PARP1 activation by binding to DNA strand break models, NAD+ substrate binding, PAR formation, and dissociation of automodified PARP1 from DNA. PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005694 chromosome | EXP PMID:33168626 The 89-kDa PARP1 cleavage fragment serves as a cytoplasmic P... | ACCEPT | Summary: PARP1 associates with chromosomes/chromatin and is recruited to damaged DNA. Reason: Well supported by chromatin binding and recruitment studies; accepted. Supporting Evidence: PMID:33168626 In the present study, we found that caspase activation by staurosporine- and actinomycin D-induced PARP1 autopoly(ADP-ribosyl)ation and fragmentation, generating poly(ADP-ribosyl)ated 89-kDa and 24-kDa PARP1 fragments. PMID:33168626 When excessive DNA damage occurs, poly(ADP-ribose) (PAR) produced by PARP1 is translocated to the cytoplasm, changing the activity and localization of cytoplasmic proteins, e.g., apoptosis-inducing factor (AIF), hexokinase, and resulting in cell death. PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. |
| GO:0005694 chromosome | EXP PMID:33412112 CARM1 regulates replication fork speed and stress response b... | ACCEPT | Summary: PARP1 associates with chromosomes/chromatin and is recruited to damaged DNA. Reason: Well supported by chromatin binding and recruitment studies; accepted. Supporting Evidence: PMID:33412112 Mechanistically, CARM1 interacts with PARP1 and promotes PARylation at replication forks. PMID:33412112 Thus, by stimulating PARP1, CARM1 slows replication forks and promotes the use of fork reversal in the stress response, revealing that CARM1 and PARP1 function as a regulatory module at forks to control fork speed and the choice of stress response mechanisms. PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. |
| GO:0005694 chromosome | EXP PMID:34625544 The regulatory landscape of the human HPF1- and ARH3-depende... | ACCEPT | Summary: PARP1 associates with chromosomes/chromatin and is recruited to damaged DNA. Reason: Well supported by chromatin binding and recruitment studies; accepted. Supporting Evidence: PMID:34625544 Our data support the notion that serine ADP-ribosylation mainly exists as mono-ADP-ribosylation in cells, and reveal a remarkable degree of histone co-modification with serine ADP-ribosylation and other post-translational modifications. PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005694 chromosome | EXP PMID:34795260 HPF1 dynamically controls the PARP1/2 balance between initia... | ACCEPT | Summary: PARP1 associates with chromosomes/chromatin and is recruited to damaged DNA. Reason: Well supported by chromatin binding and recruitment studies; accepted. Supporting Evidence: PMID:34795260 HPF1 rapidly associates/dissociates from multiple PARP1 molecules, initiating serine modification before modification initiates on glutamate/aspartate, and accelerating initiation to be more comparable to elongation reactions forming poly(ADP-ribose). PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005694 chromosome | EXP PMID:35013556 The ubiquitin-dependent ATPase p97 removes cytotoxic trapped... | ACCEPT | Summary: PARP1 associates with chromosomes/chromatin and is recruited to damaged DNA. Reason: Well supported by chromatin binding and recruitment studies; accepted. Supporting Evidence: PMID:35013556 We found that following trapping, PARP1 is SUMOylated by PIAS4 and subsequently ubiquitylated by the SUMO-targeted E3 ubiquitin ligase RNF4, events that promote recruitment of p97 and removal of trapped PARP1 from chromatin. PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005694 chromosome | EXP PMID:35104452 SPARCLE, a p53-induced lncRNA, controls apoptosis after geno... | ACCEPT | Summary: PARP1 associates with chromosomes/chromatin and is recruited to damaged DNA. Reason: Well supported by chromatin binding and recruitment studies; accepted. Supporting Evidence: PMID:35104452 SPARCLE binds to PARP-1 with nanomolar affinity and causes apoptosis by acting as a caspase-3 cofactor for PARP-1 cleavage, which separates PARP-1's N-terminal (NT) DNA-binding domain from its catalytic domains. PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005694 chromosome | EXP PMID:9721847 Irreversible binding of poly(ADP)ribose polymerase cleavage ... | ACCEPT | Summary: PARP1 associates with chromosomes/chromatin and is recruited to damaged DNA. Reason: Well supported by chromatin binding and recruitment studies; accepted. Supporting Evidence: PMID:9721847 Atomic force microscopy revealed that recombinant full-length PARP bound to plasmid DNA fragments and linked them into chainlike structures. PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005694 chromosome | IEA GO_REF:0000044 | ACCEPT | Summary: PARP1 associates with chromosomes/chromatin and is recruited to damaged DNA. Reason: Well supported by chromatin binding and recruitment studies; accepted. Supporting Evidence: PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0005730 nucleolus | IBA GO_REF:0000033 | ACCEPT | Summary: PARP1 is enriched in the nucleolus in undamaged cells and redistributes to the nucleoplasm upon DNA damage. Reason: Nucleolar localization is reproducibly observed (immunofluorescence, HPA, IBA). Supporting Evidence: PMID:16107709 We find that CSB is present at sites of activated PARP-1 after oxidative stress, identify CSB as a new substrate of PARP-1, and demonstrate that poly(ADP-ribosyl)ation of CSB inhibits its DNA-dependent ATPase activity. PMID:9518481 Altogether, the present results strongly suggest that PARP participates in a DNA damage survey mechanism implying its nick-sensor function as part of the control of replication fork progression when breaks are present in the template. |
| GO:0005730 nucleolus | IDA GO_REF:0000052 | ACCEPT | Summary: PARP1 is enriched in the nucleolus in undamaged cells and redistributes to the nucleoplasm upon DNA damage. Reason: Nucleolar localization is reproducibly observed (immunofluorescence, HPA, IBA). Supporting Evidence: PMID:16107709 We find that CSB is present at sites of activated PARP-1 after oxidative stress, identify CSB as a new substrate of PARP-1, and demonstrate that poly(ADP-ribosyl)ation of CSB inhibits its DNA-dependent ATPase activity. PMID:9518481 Altogether, the present results strongly suggest that PARP participates in a DNA damage survey mechanism implying its nick-sensor function as part of the control of replication fork progression when breaks are present in the template. |
| GO:0005730 nucleolus | IDA PMID:16107709 Cooperation of the Cockayne syndrome group B protein and pol... | ACCEPT | Summary: PARP1 is enriched in the nucleolus in undamaged cells and redistributes to the nucleoplasm upon DNA damage. Reason: Nucleolar localization is reproducibly observed (immunofluorescence, HPA, IBA). Supporting Evidence: PMID:16107709 We find that CSB is present at sites of activated PARP-1 after oxidative stress, identify CSB as a new substrate of PARP-1, and demonstrate that poly(ADP-ribosyl)ation of CSB inhibits its DNA-dependent ATPase activity. PMID:9518481 Altogether, the present results strongly suggest that PARP participates in a DNA damage survey mechanism implying its nick-sensor function as part of the control of replication fork progression when breaks are present in the template. |
| GO:0005730 nucleolus | IDA PMID:9518481 Functional association of poly(ADP-ribose) polymerase with D... | ACCEPT | Summary: PARP1 is enriched in the nucleolus in undamaged cells and redistributes to the nucleoplasm upon DNA damage. Reason: Nucleolar localization is reproducibly observed (immunofluorescence, HPA, IBA). Supporting Evidence: PMID:9518481 Altogether, the present results strongly suggest that PARP participates in a DNA damage survey mechanism implying its nick-sensor function as part of the control of replication fork progression when breaks are present in the template. PMID:16107709 We find that CSB is present at sites of activated PARP-1 after oxidative stress, identify CSB as a new substrate of PARP-1, and demonstrate that poly(ADP-ribosyl)ation of CSB inhibits its DNA-dependent ATPase activity. |
| GO:0005730 nucleolus | IEA GO_REF:0000044 | ACCEPT | Summary: PARP1 is enriched in the nucleolus in undamaged cells and redistributes to the nucleoplasm upon DNA damage. Reason: Nucleolar localization is reproducibly observed (immunofluorescence, HPA, IBA). Supporting Evidence: PMID:16107709 We find that CSB is present at sites of activated PARP-1 after oxidative stress, identify CSB as a new substrate of PARP-1, and demonstrate that poly(ADP-ribosyl)ation of CSB inhibits its DNA-dependent ATPase activity. PMID:9518481 Altogether, the present results strongly suggest that PARP participates in a DNA damage survey mechanism implying its nick-sensor function as part of the control of replication fork progression when breaks are present in the template. |
| GO:0005737 cytoplasm | EXP PMID:33168626 The 89-kDa PARP1 cleavage fragment serves as a cytoplasmic P... | KEEP AS NON CORE | Summary: A fraction of PARP1 (or its caspase-generated 89 kDa fragment) is found in the cytoplasm. Reason: Cytoplasmic PARP1 is reported under specific conditions (apoptosis; DNA-PK-phosphorylated PARP1 in innate immunity). Non-core. Supporting Evidence: PMID:33168626 In the present study, we found that caspase activation by staurosporine- and actinomycin D-induced PARP1 autopoly(ADP-ribosyl)ation and fragmentation, generating poly(ADP-ribosyl)ated 89-kDa and 24-kDa PARP1 fragments. PMID:33168626 When excessive DNA damage occurs, poly(ADP-ribose) (PAR) produced by PARP1 is translocated to the cytoplasm, changing the activity and localization of cytoplasmic proteins, e.g., apoptosis-inducing factor (AIF), hexokinase, and resulting in cell death. PMID:35460603 Activated DNA-PK phosphorylates PARP1 on Thr594, thus facilitating the cytoplasmic translocation of PARP1 to inhibit the antiviral immunity both in vitro and in vivo. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: A fraction of PARP1 (or its caspase-generated 89 kDa fragment) is found in the cytoplasm. Reason: Cytoplasmic PARP1 is reported under specific conditions (apoptosis; DNA-PK-phosphorylated PARP1 in innate immunity). Non-core. Supporting Evidence: PMID:33168626 In the present study, we found that caspase activation by staurosporine- and actinomycin D-induced PARP1 autopoly(ADP-ribosyl)ation and fragmentation, generating poly(ADP-ribosyl)ated 89-kDa and 24-kDa PARP1 fragments. PMID:35460603 Activated DNA-PK phosphorylates PARP1 on Thr594, thus facilitating the cytoplasmic translocation of PARP1 to inhibit the antiviral immunity both in vitro and in vivo. |
| GO:0005739 mitochondrion | IDA PMID:25378300 Opposing roles of mitochondrial and nuclear PARP1 in the reg... | KEEP AS NON CORE | Summary: A pool of PARP1 is reported inside mitochondria, where it interacts with mitochondrial DNA repair factors. Reason: Mitochondrial PARP1 is reported but contested; non-core. Supporting Evidence: PMID:25378300 Our data show that intra-mitochondrial PARP1 interacts with a key mitochondrial-specific DNA base excision repair (BER) enzymes, namely EXOG and DNA polymerase gamma (PolΞ³), which under oxidative stress become poly(ADP-ribose)lated (PARylated). PMID:25378300 In summary, we conclude that mitochondrial PARP1, in opposite to nuclear PARP1, exerts a negative effect on several mitochondrial-specific transactions including the repair of the mitochondrial DNA. |
| GO:0005829 cytosol | IDA PMID:35460603 Cytoplasmic PARP1 links the genome instability to the inhibi... | KEEP AS NON CORE | Summary: Cytoplasmic PARP1 translocated after DNA-PK phosphorylation PARylates cGAS in the cytosol. Reason: Condition-specific localization; non-core. Supporting Evidence: PMID:35460603 Activated DNA-PK phosphorylates PARP1 on Thr594, thus facilitating the cytoplasmic translocation of PARP1 to inhibit the antiviral immunity both in vitro and in vivo. PMID:35460603 Mechanistically, cytoplasmic PARP1 interacts with and directly PARylates cyclic GMP-AMP synthase (cGAS) on Asp191 to inhibit its DNA-binding ability. |
| GO:0005829 cytosol | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Cytoplasmic PARP1 translocated after DNA-PK phosphorylation PARylates cGAS in the cytosol. Reason: Condition-specific localization; non-core. Supporting Evidence: PMID:35460603 Activated DNA-PK phosphorylates PARP1 on Thr594, thus facilitating the cytoplasmic translocation of PARP1 to inhibit the antiviral immunity both in vitro and in vivo. |
| GO:0006281 DNA repair | IDA PMID:30104678 PARP2 mediates branched poly ADP-ribosylation in response to... | ACCEPT | Summary: PARP1 participates in DNA repair (single-strand break, base excision and double-strand break repair) as a damage sensor and PAR-synthesising signalling enzyme. Reason: Core process; supported by many studies including repair deficiency in PARP-deficient cells. Supporting Evidence: PMID:30104678 Once DNA damage occurs, PARP1 is immediately recruited to the damaged DNA ends through its N-terminal DNA-binding motif, and stimulates PARylation via its C-terminal enzymatic domain20,21. PMID:10958667 Poly(ADP-ribose) polymerase (PARP) is a DNA binding zinc finger protein that catalyzes the transfer of ADP-ribose residues from NAD(+) to itself and different chromatin constituents, forming branched ADP-ribose polymers. PMID:34102106 PARPs are sensors that detect single-strand break intermediates, but the critical role of XRCC1 during BER is unknown. |
| GO:0006281 DNA repair | IDA PMID:30675909 Increased PARP1-DNA binding due to autoPARylation inhibition... | ACCEPT | Summary: PARP1 participates in DNA repair (single-strand break, base excision and double-strand break repair) as a damage sensor and PAR-synthesising signalling enzyme. Reason: Core process; supported by many studies including repair deficiency in PARP-deficient cells. Supporting Evidence: PMID:30675909 PARP1 inhibitors (PARPis) are used clinically during cancer therapy and are thought to exert their cytotoxicity through PARP1 polymerase inhibition and PARP1-DNA trapping. PMID:10958667 Poly(ADP-ribose) polymerase (PARP) is a DNA binding zinc finger protein that catalyzes the transfer of ADP-ribose residues from NAD(+) to itself and different chromatin constituents, forming branched ADP-ribose polymers. PMID:34102106 PARPs are sensors that detect single-strand break intermediates, but the critical role of XRCC1 during BER is unknown. |
| GO:0006281 DNA repair | IDA PMID:31796734 Barrier-to-autointegration factor 1 (Banf1) regulates poly [... | ACCEPT | Summary: PARP1 participates in DNA repair (single-strand break, base excision and double-strand break repair) as a damage sensor and PAR-synthesising signalling enzyme. Reason: Core process; supported by many studies including repair deficiency in PARP-deficient cells. Supporting Evidence: PMID:31796734 Specifically, oxidative lesions promote direct binding of Banf1 to PARP1, a critical NAD+-dependent DNA repair protein, leading to inhibition of PARP1 auto-ADP-ribosylation and defective repair of oxidative lesions, in cells with increased Banf1. PMID:10958667 Poly(ADP-ribose) polymerase (PARP) is a DNA binding zinc finger protein that catalyzes the transfer of ADP-ribose residues from NAD(+) to itself and different chromatin constituents, forming branched ADP-ribose polymers. PMID:34102106 PARPs are sensors that detect single-strand break intermediates, but the critical role of XRCC1 during BER is unknown. |
| GO:0006281 DNA repair | IDA PMID:32028527 HPF1 completes the PARP active site for DNA damage-induced A... | ACCEPT | Summary: PARP1 participates in DNA repair (single-strand break, base excision and double-strand break repair) as a damage sensor and PAR-synthesising signalling enzyme. Reason: Core process; supported by many studies including repair deficiency in PARP-deficient cells. Supporting Evidence: PMID:32028527 After binding to genomic lesions, these enzymes use NAD+ to modify numerous proteins with mono- and poly(ADP-ribose) signals that are important for the subsequent decompaction of chromatin and the recruitment of repair factors3,4. PMID:32028527 These post-translational modifications are predominantly serine-linked and require the accessory factor HPF1, which is specific for the DNA damage response and switches the amino acid specificity of PARP1 and PARP2 from aspartate or glutamate to serine residues5-10. PMID:10958667 Poly(ADP-ribose) polymerase (PARP) is a DNA binding zinc finger protein that catalyzes the transfer of ADP-ribose residues from NAD(+) to itself and different chromatin constituents, forming branched ADP-ribose polymers. |
| GO:0006281 DNA repair | IDA PMID:33186521 An HPF1/PARP1-Based Chemical Biology Strategy for Exploring ... | ACCEPT | Summary: PARP1 participates in DNA repair (single-strand break, base excision and double-strand break repair) as a damage sensor and PAR-synthesising signalling enzyme. Reason: Core process; supported by many studies including repair deficiency in PARP-deficient cells. Supporting Evidence: PMID:33186521 An HPF1/PARP1-Based Chemical Biology Strategy for Exploring ADP-Ribosylation. PMID:10958667 Poly(ADP-ribose) polymerase (PARP) is a DNA binding zinc finger protein that catalyzes the transfer of ADP-ribose residues from NAD(+) to itself and different chromatin constituents, forming branched ADP-ribose polymers. PMID:34102106 PARPs are sensors that detect single-strand break intermediates, but the critical role of XRCC1 during BER is unknown. |
| GO:0006281 DNA repair | IDA PMID:34874266 Serine ADP-ribosylation marks nucleosomes for ALC1-dependent... | ACCEPT | Summary: PARP1 participates in DNA repair (single-strand break, base excision and double-strand break repair) as a damage sensor and PAR-synthesising signalling enzyme. Reason: Core process; supported by many studies including repair deficiency in PARP-deficient cells. Supporting Evidence: PMID:34874266 Serine ADP-ribosylation (ADPr) is a DNA damage-induced post-translational modification catalyzed by the PARP1/2:HPF1 complex. PMID:34874266 This chemoenzymatic protein synthesis strategy was employed to assemble a series of full-length, ADP-ribosylated histones and show that ADPr at histone H2B serine 6 or histone H3 serine 10 converts nucleosomes into robust substrates for the chromatin remodeler ALC1. PMID:10958667 Poly(ADP-ribose) polymerase (PARP) is a DNA binding zinc finger protein that catalyzes the transfer of ADP-ribose residues from NAD(+) to itself and different chromatin constituents, forming branched ADP-ribose polymers. |
| GO:0006281 DNA repair | TAS PMID:10958667 DNA excision repair and DNA damage-induced apoptosis are lin... | ACCEPT | Summary: PARP1 participates in DNA repair (single-strand break, base excision and double-strand break repair) as a damage sensor and PAR-synthesising signalling enzyme. Reason: Core process; supported by many studies including repair deficiency in PARP-deficient cells. Supporting Evidence: PMID:10958667 Poly(ADP-ribose) polymerase (PARP) is a DNA binding zinc finger protein that catalyzes the transfer of ADP-ribose residues from NAD(+) to itself and different chromatin constituents, forming branched ADP-ribose polymers. PMID:10958667 DNA repair is almost completely blocked in PARP-deficient thymocytes regardless of p53 status. PMID:34102106 PARPs are sensors that detect single-strand break intermediates, but the critical role of XRCC1 during BER is unknown. |
| GO:0006281 DNA repair | TAS PMID:17396150 A novel human AP endonuclease with conserved zinc-finger-lik... | ACCEPT | Summary: PARP1 participates in DNA repair (single-strand break, base excision and double-strand break repair) as a damage sensor and PAR-synthesising signalling enzyme. Reason: Core process; supported by many studies including repair deficiency in PARP-deficient cells. Supporting Evidence: PMID:17396150 In mammalian cells, it has been shown in vitro and in vivo that SSBs activate poly(ADP-ribose) polymerases (PARP), which poly(ADP-ribosyl)ate proteins near SSBs as well as PARP itself. PMID:17396150 Indeed, PALF interacts directly with PARP1 and is required for its activation and for cellular resistance to methyl-methane sulfonate. PMID:10958667 Poly(ADP-ribose) polymerase (PARP) is a DNA binding zinc finger protein that catalyzes the transfer of ADP-ribose residues from NAD(+) to itself and different chromatin constituents, forming branched ADP-ribose polymers. |
| GO:0006302 double-strand break repair | IBA GO_REF:0000033 | ACCEPT | Summary: PARP1 is recruited to DSBs and its PAR synthesis recruits repair factors (e.g. Timeless, PARP9/DTX3L, SIRT6) contributing to double-strand break repair. Reason: Core process, supported by IBA and by direct recruitment/mechanistic studies. Supporting Evidence: PMID:26344098 We demonstrate that rapid and transient accumulation of Timeless at laser-induced DNA damage sites requires PARP-1, but not poly(ADP-ribosyl)ation and that Timeless is co-trapped with PARP-1 at DNA lesions upon PARP inhibition. PMID:23230272 These data establish that BAL1 and BBAP are bona fide members of a DNA damage response pathway and are directly associated with PARP1 activation, BRCA1 recruitment, and double-strand break repair. |
| GO:0006302 double-strand break repair | IDA PMID:24906880 PARG is dispensable for recovery from transient replicative ... | ACCEPT | Summary: PARP1 is recruited to DSBs and its PAR synthesis recruits repair factors (e.g. Timeless, PARP9/DTX3L, SIRT6) contributing to double-strand break repair. Reason: Core process, supported by IBA and by direct recruitment/mechanistic studies. Supporting Evidence: PMID:24906880 The founding member of the PARP family PARP-1 is a key regulator of DNA damage repair, by controlling the recruitment or repellence of DNA repair enzymes as well as chromatin structure modifiers to accelerate repair (1,2). PMID:26344098 We demonstrate that rapid and transient accumulation of Timeless at laser-induced DNA damage sites requires PARP-1, but not poly(ADP-ribosyl)ation and that Timeless is co-trapped with PARP-1 at DNA lesions upon PARP inhibition. PMID:23230272 These data establish that BAL1 and BBAP are bona fide members of a DNA damage response pathway and are directly associated with PARP1 activation, BRCA1 recruitment, and double-strand break repair. |
| GO:0006302 double-strand break repair | IDA PMID:27568560 JNK Phosphorylates SIRT6 to Stimulate DNA Double-Strand Brea... | ACCEPT | Summary: PARP1 is recruited to DSBs and its PAR synthesis recruits repair factors (e.g. Timeless, PARP9/DTX3L, SIRT6) contributing to double-strand break repair. Reason: Core process, supported by IBA and by direct recruitment/mechanistic studies. Supporting Evidence: PMID:27568560 This post-translational modification facilitates the mobilization of SIRT6 to DNA damage sites and is required for efficient recruitment of poly (ADP-ribose) polymerase 1 (PARP1) to DNA break sites and for efficient repair of DSBs. PMID:26344098 We demonstrate that rapid and transient accumulation of Timeless at laser-induced DNA damage sites requires PARP-1, but not poly(ADP-ribosyl)ation and that Timeless is co-trapped with PARP-1 at DNA lesions upon PARP inhibition. PMID:23230272 These data establish that BAL1 and BBAP are bona fide members of a DNA damage response pathway and are directly associated with PARP1 activation, BRCA1 recruitment, and double-strand break repair. |
| GO:0006302 double-strand break repair | IDA PMID:28190768 Serine ADP-Ribosylation Depends on HPF1. | ACCEPT | Summary: PARP1 is recruited to DSBs and its PAR synthesis recruits repair factors (e.g. Timeless, PARP9/DTX3L, SIRT6) contributing to double-strand break repair. Reason: Core process, supported by IBA and by direct recruitment/mechanistic studies. Supporting Evidence: PMID:28190768 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. PMID:28190768 Moreover, adding HPF1 to in vitro PARP-1/PARP-2 reactions is necessary and sufficient for serine-specific ADPr of histones and PARP-1 itself. PMID:26344098 We demonstrate that rapid and transient accumulation of Timeless at laser-induced DNA damage sites requires PARP-1, but not poly(ADP-ribosyl)ation and that Timeless is co-trapped with PARP-1 at DNA lesions upon PARP inhibition. |
| GO:0006302 double-strand break repair | IMP PMID:23230272 BAL1 and its partner E3 ligase, BBAP, link Poly(ADP-ribose) ... | ACCEPT | Summary: PARP1 is recruited to DSBs and its PAR synthesis recruits repair factors (e.g. Timeless, PARP9/DTX3L, SIRT6) contributing to double-strand break repair. Reason: Core process, supported by IBA and by direct recruitment/mechanistic studies. Supporting Evidence: PMID:23230272 These data establish that BAL1 and BBAP are bona fide members of a DNA damage response pathway and are directly associated with PARP1 activation, BRCA1 recruitment, and double-strand break repair. PMID:26344098 We demonstrate that rapid and transient accumulation of Timeless at laser-induced DNA damage sites requires PARP-1, but not poly(ADP-ribosyl)ation and that Timeless is co-trapped with PARP-1 at DNA lesions upon PARP inhibition. |
| GO:0006366 transcription by RNA polymerase II | TAS PMID:10944198 A cellular defense pathway regulating transcription through ... | KEEP AS NON CORE | Summary: PARP1 affects transcription elongation by RNA polymerase II. Reason: The cited study shows PARP reduced the rate of elongation; regulatory, non-core. Supporting Evidence: PMID:10944198 We found that poly(ADP-ribose) polymerase reduced the rate of transcription elongation by RNA polymerase II, suggesting that poly(ADP-ribose) polymerase negatively regulates transcription, possibly through the formation of poly(ADP-ribose) polymerase-RNA complexes. |
| GO:0006915 apoptotic process | IDA PMID:15565177 A novel mitochondrial protein DIP mediates E2F1-induced apop... | MARK AS OVER ANNOTATED | Summary: Apoptotic process annotation from a study where PARP1 cleavage served as an apoptosis marker. Reason: In the cited study PARP cleavage is a readout of caspase activity during DIP/E2F1-induced apoptosis; PARP1 is the caspase substrate and does not execute the apoptotic process. Experimental row, so flagged as over-annotation rather than removed. Supporting Evidence: PMID:15565177 DIP greatly reduced cell viability in several in vitro systems accompanied by typical apoptotic features such as caspase-3 activation and cleavage of poly(ADP-ribose)-polymerase. |
| GO:0006974 DNA damage response | IDA PMID:22683995 The zinc-finger domains of PARP1 cooperate to recognize DNA ... | ACCEPT | Summary: PARP1 is a primary DNA damage sensor whose activity drives the cellular response to DNA damage. Reason: Core process; PARP1 activation at breaks initiates PAR-dependent recruitment of repair and chromatin factors. Supporting Evidence: PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. PMID:22683995 Upon activation at sites of DNA damage, PARP1 modifies itself and other proteins by covalent addition of long, branched polymers of ADP-ribose, which in turn recruit downstream DNA repair and chromatin remodeling factors. |
| GO:0006974 DNA damage response | IDA PMID:32358582 Real-time monitoring of PARP1-dependent PARylation by ATR-FT... | ACCEPT | Summary: PARP1 is a primary DNA damage sensor whose activity drives the cellular response to DNA damage. Reason: Core process; PARP1 activation at breaks initiates PAR-dependent recruitment of repair and chromatin factors. Supporting Evidence: PMID:32358582 This includes PARP1 activation by binding to DNA strand break models, NAD+ substrate binding, PAR formation, and dissociation of automodified PARP1 from DNA. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0006974 DNA damage response | IDA PMID:35013556 The ubiquitin-dependent ATPase p97 removes cytotoxic trapped... | ACCEPT | Summary: PARP1 is a primary DNA damage sensor whose activity drives the cellular response to DNA damage. Reason: Core process; PARP1 activation at breaks initiates PAR-dependent recruitment of repair and chromatin factors. Supporting Evidence: PMID:35013556 We found that following trapping, PARP1 is SUMOylated by PIAS4 and subsequently ubiquitylated by the SUMO-targeted E3 ubiquitin ligase RNF4, events that promote recruitment of p97 and removal of trapped PARP1 from chromatin. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0006974 DNA damage response | IDA PMID:35393539 Poly(ADP-ribosylation) of P-TEFb by PARP1 disrupts phase sep... | ACCEPT | Summary: PARP1 is a primary DNA damage sensor whose activity drives the cellular response to DNA damage. Reason: Core process; PARP1 activation at breaks initiates PAR-dependent recruitment of repair and chromatin factors. Supporting Evidence: PMID:35393539 Here we report that PARP1 inhibits Pol II elongation by inactivating the transcription elongation factor P-TEFb, a CDK9-cyclin T1 (CycT1) heterodimer. PMID:35393539 After sensing damage, the activated PARP1 binds to transcriptionally engaged P-TEFb and modifies CycT1 at multiple positions, including histidine residues that are rarely used as an acceptor site. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0006974 DNA damage response | IDA PMID:37823600 ZNF432 stimulates PARylation and inhibits DNA resection to b... | ACCEPT | Summary: PARP1 is a primary DNA damage sensor whose activity drives the cellular response to DNA damage. Reason: Core process; PARP1 activation at breaks initiates PAR-dependent recruitment of repair and chromatin factors. Supporting Evidence: PMID:37823600 Remarkably, ZNF432 stimulates PARP-1 activity in vitro and in cellulo. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0006974 DNA damage response | IEA GO_REF:0000120 | ACCEPT | Summary: PARP1 is a primary DNA damage sensor whose activity drives the cellular response to DNA damage. Reason: Core process; PARP1 activation at breaks initiates PAR-dependent recruitment of repair and chromatin factors. Supporting Evidence: PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0006974 DNA damage response | IMP PMID:24289924 Phosphorylation of p53 by TAF1 inactivates p53-dependent tra... | ACCEPT | Summary: PARP1 is a primary DNA damage sensor whose activity drives the cellular response to DNA damage. Reason: Core process; PARP1 activation at breaks initiates PAR-dependent recruitment of repair and chromatin factors. Supporting Evidence: PMID:24289924 Upon DNA damage, cells undergo PARP-1-dependent ATP depletion, which is correlated with reduced TAF1 kinase activity and Thr55 phosphorylation, resulting in p21 activation. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0006974 DNA damage response | IMP PMID:24550317 PARP1-dependent recruitment of KDM4D histone demethylase to ... | ACCEPT | Summary: PARP1 is a primary DNA damage sensor whose activity drives the cellular response to DNA damage. Reason: Core process; PARP1 activation at breaks initiates PAR-dependent recruitment of repair and chromatin factors. Supporting Evidence: PMID:24550317 Interestingly, this recruitment is independent of the DDR sensor ataxia telangiectasia mutated (ATM), but dependent on poly (ADP-ribose) polymerase 1 (PARP1), which ADP ribosylates KDM4D after damage. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0006974 DNA damage response | IMP PMID:27067600 HPF1/C4orf27 Is a PARP-1-Interacting Protein that Regulates ... | ACCEPT | Summary: PARP1 is a primary DNA damage sensor whose activity drives the cellular response to DNA damage. Reason: Core process; PARP1 activation at breaks initiates PAR-dependent recruitment of repair and chromatin factors. Supporting Evidence: PMID:27067600 Functionally, HPF1 promotes PARP-1-dependent in trans ADP-ribosylation of histones and limits DNA damage-induced hyper-automodification of PARP-1. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0006974 DNA damage response | IMP PMID:27248496 WDR76 Co-Localizes with Heterochromatin Related Proteins and... | ACCEPT | Summary: PARP1 is a primary DNA damage sensor whose activity drives the cellular response to DNA damage. Reason: Core process; PARP1 activation at breaks initiates PAR-dependent recruitment of repair and chromatin factors. Supporting Evidence: PMID:27248496 Next, quantitative imaging studies demonstrated that WDR76 was recruited to laser induced DNA damage immediately after induction, and we compared the recruitment of WDR76 to laser induced DNA damage to known DNA damage proteins like PARP1, XRCC5, and RPA1. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0007005 mitochondrion organization | IMP PMID:25378300 Opposing roles of mitochondrial and nuclear PARP1 in the reg... | KEEP AS NON CORE | Summary: PARP1 depletion affects mitochondrial organization/function. Reason: Indirect phenotype; non-core. Supporting Evidence: PMID:25378300 Our data show that intra-mitochondrial PARP1 interacts with a key mitochondrial-specific DNA base excision repair (BER) enzymes, namely EXOG and DNA polymerase gamma (PolΞ³), which under oxidative stress become poly(ADP-ribose)lated (PARylated). PMID:25378300 In summary, we conclude that mitochondrial PARP1, in opposite to nuclear PARP1, exerts a negative effect on several mitochondrial-specific transactions including the repair of the mitochondrial DNA. |
| GO:0007179 transforming growth factor beta receptor signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog projection: PARP1 modulates TGF-beta signalling by ADP-ribosylating SMADs. Reason: PARP1 modulates SMAD-dependent transcription; non-core. |
| GO:0008047 enzyme activator activity | IDA PMID:25749521 TNKS1BP1 functions in DNA double-strand break repair though ... | KEEP AS NON CORE | Summary: PARP1 is required for TNKS1BP1-facilitated DNA-PKcs autophosphorylation in DSB repair. Reason: The study shows PARP1-dependent stimulation of DNA-PKcs autophosphorylation; consistent with PARP1 promoting DNA-PK activity, but a context-specific role rather than core function. Kept as non-core. Supporting Evidence: PMID:25749521 The TNKS1BP1 protein was demonstrated to interact with DNA-dependent protein kinase (DNA-PKcs) and poly(ADP-ribose) polymerase 1 (PARP-1), by co-immunoprecipitation analysis. |
| GO:0008270 zinc ion binding | IDA PMID:18055453 A third zinc-binding domain of human poly(ADP-ribose) polyme... | ACCEPT | Summary: PARP1 contains three zinc-binding domains (Zn1, Zn2 PARP-type zinc fingers and Zn3). Reason: Structural and spectroscopic evidence shows zinc coordination by the zinc fingers, which are required for DNA-dependent activation. Supporting Evidence: PMID:18055453 Here, we demonstrate using spectroscopic and crystallographic analysis that human PARP-1 has a third zinc-binding domain. PMID:18055453 Two zinc finger domains at the N terminus of PARP-1 bind to DNA and thereby activate the catalytic domain situated at the C terminus of the enzyme. PMID:21233213 Poly(ADP-ribose) polymerase-1 (PARP-1) has two homologous zinc finger domains, Zn1 and Zn2, that bind to a variety of DNA structures to stimulate poly(ADP-ribose) synthesis activity and to mediate PARP-1 interaction with chromatin. |
| GO:0008270 zinc ion binding | IDA PMID:21233213 Crystal structures of poly(ADP-ribose) polymerase-1 (PARP-1)... | ACCEPT | Summary: PARP1 contains three zinc-binding domains (Zn1, Zn2 PARP-type zinc fingers and Zn3). Reason: Structural and spectroscopic evidence shows zinc coordination by the zinc fingers, which are required for DNA-dependent activation. Supporting Evidence: PMID:21233213 Poly(ADP-ribose) polymerase-1 (PARP-1) has two homologous zinc finger domains, Zn1 and Zn2, that bind to a variety of DNA structures to stimulate poly(ADP-ribose) synthesis activity and to mediate PARP-1 interaction with chromatin. PMID:18055453 Here, we demonstrate using spectroscopic and crystallographic analysis that human PARP-1 has a third zinc-binding domain. |
| GO:0008270 zinc ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: PARP1 contains three zinc-binding domains (Zn1, Zn2 PARP-type zinc fingers and Zn3). Reason: Structural and spectroscopic evidence shows zinc coordination by the zinc fingers, which are required for DNA-dependent activation. Supporting Evidence: PMID:18055453 Here, we demonstrate using spectroscopic and crystallographic analysis that human PARP-1 has a third zinc-binding domain. PMID:21233213 Poly(ADP-ribose) polymerase-1 (PARP-1) has two homologous zinc finger domains, Zn1 and Zn2, that bind to a variety of DNA structures to stimulate poly(ADP-ribose) synthesis activity and to mediate PARP-1 interaction with chromatin. |
| GO:0010332 response to gamma radiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog projection: response to gamma radiation. Reason: Consistent with PARP1 activation by radiation-induced DNA breaks; non-core. Supporting Evidence: PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0010613 positive regulation of cardiac muscle hypertrophy | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of cardiac muscle hypertrophy (ortholog projection/ISS). Reason: PARP1 activation in stressed cardiomyocytes contributes to hypertrophy in rodent models; an organ-level phenotype of NAD+ consumption rather than a PARP1 function. Over-annotation. Supporting Evidence: PMID:19470756 Here, we show that PARP1 is acetylated after stress of cardiomyocytes, resulting in the activation of PARP1, which is independent of DNA damage. |
| GO:0010613 positive regulation of cardiac muscle hypertrophy | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Positive regulation of cardiac muscle hypertrophy (ortholog projection/ISS). Reason: PARP1 activation in stressed cardiomyocytes contributes to hypertrophy in rodent models; an organ-level phenotype of NAD+ consumption rather than a PARP1 function. Over-annotation. Supporting Evidence: PMID:19470756 Here, we show that PARP1 is acetylated after stress of cardiomyocytes, resulting in the activation of PARP1, which is independent of DNA damage. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: PARP1 was detected in a membrane proteome of an NK-like cell line. Reason: Detection of an abundant nuclear protein in a membrane-enriched proteomic fraction most likely reflects co-purification; there is no evidence that PARP1 functions at membranes. Experimental (HDA), so flagged as over-annotation rather than removed. |
| GO:0016051 carbohydrate biosynthetic process | IEA GO_REF:0000107 | REMOVE | Summary: Electronic ortholog projection to carbohydrate biosynthetic process. Reason: PAR synthesis is captured by GO:0003950; describing PARP1 as acting in carbohydrate biosynthesis is a misleading electronic projection with no supporting evidence. |
| GO:0016540 protein autoprocessing | IEA GO_REF:0000107 | REMOVE | Summary: Electronic ortholog projection of protein autoprocessing. Reason: PARP1 is cleaved by caspases-3/7 (and other proteases) during cell death; it does not cleave itself. Protein autoprocessing requires the gene product to process itself, so this term is incorrect for PARP1. |
| GO:0016604 nuclear body | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Human Protein Atlas immunofluorescence localizes PARP1 to nuclear bodies. Reason: High-throughput localization; non-core. |
| GO:0019899 enzyme binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: PARP1 binds various enzymes (e.g. in large-scale interaction studies). Reason: Enzyme binding is a generic, low-information term. The IEA ortholog projection adds nothing; the experimental row is kept as non-core. |
| GO:0019899 enzyme binding | IPI PMID:23382074 A high-confidence interaction map identifies SIRT1 as a medi... | KEEP AS NON CORE | Summary: PARP1 binds various enzymes (e.g. in large-scale interaction studies). Reason: Enzyme binding is a generic, low-information term. The IEA ortholog projection adds nothing; the experimental row is kept as non-core. Supporting Evidence: PMID:23382074 Using a comparative statistical analysis of binding partners, we have assembled a high-confidence SIRT1 interactome. |
| GO:0019901 protein kinase binding | IPI PMID:17177976 Txk, a member of the non-receptor tyrosine kinase of the Tec... | KEEP AS NON CORE | Summary: PARP1 forms a complex with the Tec kinase Txk and EF-1alpha in T cells. Reason: Experimental interaction with a kinase in a specialised T-cell context; non-core. Supporting Evidence: PMID:17177976 Upon activation, a complex involving Txk, EF-1alpha and PARP1 was formed and was located in the nucleus. PMID:17177976 Txk phosphorylated EF-1alpha and PARP1 formed a complex with them, and bound to the IFN-gamma gene promoter in vitro. |
| GO:0023019 signal transduction involved in regulation of gene expression | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Electronic ortholog projection to signal transduction involved in regulation of gene expression. Reason: Vague term not adding information beyond the transcription regulation annotations. |
| GO:0030225 macrophage differentiation | TAS PMID:18309324 No death without life: vital functions of apoptotic effector... | MARK AS OVER ANNOTATED | Summary: Macrophage differentiation attributed to PARP1 in a review of non-apoptotic caspase functions. Reason: The review concerns vital functions of apoptotic effectors (caspases); PARP1 appears as a caspase substrate cleaved during differentiation rather than as an agent of macrophage differentiation. Supporting Evidence: PMID:18309324 However, multiple studies indicate that the mammalian orthologs of these C. elegans proteins (i.e. caspases, Apaf-1 and multidomain proteins of the Bcl-2 family) participate in cell death-unrelated processes. |
| GO:0030331 obsolete nuclear estrogen receptor binding | IEA GO_REF:0000107 | MODIFY | Summary: PARP1 binds and coactivates estrogen receptor alpha; the original term is obsolete. Reason: GO:0030331 is obsolete (QuickGO: obsoleted because it represents a gene product; consider GO:0016922 nuclear receptor binding). Replace with GO:0016922; non-core. Proposed replacements: nuclear receptor binding |
| GO:0030592 obsolete DNA ADP-ribosylation | IDA PMID:27471034 Poly(ADP-ribose) polymerases covalently modify strand break ... | MODIFY | Summary: PARP1 ADP-ribosylates DNA strand-break ends in vitro. Reason: GO:0030592 DNA ADP-ribosylation is obsolete (QuickGO: represents a molecular function; consider GO:0140294). Replace with GO:0140294 NAD DNA ADP-ribosyltransferase activity (non-core). Proposed replacements: NAD DNA ADP-ribosyltransferase activity Supporting Evidence: PMID:27471034 Here, in in vitro biochemical experiments, we found that the mammalian PARP1 and PARP2 proteins can directly ADP-ribosylate the termini of DNA oligonucleotides. PMID:27471034 PARP1 preferentially catalysed covalent attachment of ADP-ribose units to the ends of recessed DNA duplexes containing 3'-cordycepin, 5'- and 3'-phosphate and also to 5'-phosphate of a single-stranded oligonucleotide. |
| GO:0030592 obsolete DNA ADP-ribosylation | IEA GO_REF:0000117 | MODIFY | Summary: PARP1 ADP-ribosylates DNA strand-break ends in vitro. Reason: GO:0030592 DNA ADP-ribosylation is obsolete (QuickGO: represents a molecular function; consider GO:0140294). Replace with GO:0140294 NAD DNA ADP-ribosyltransferase activity (non-core). Proposed replacements: NAD DNA ADP-ribosyltransferase activity Supporting Evidence: PMID:27471034 Here, in in vitro biochemical experiments, we found that the mammalian PARP1 and PARP2 proteins can directly ADP-ribosylate the termini of DNA oligonucleotides. |
| GO:0031491 nucleosome binding | IDA PMID:15607977 NAD+-dependent modulation of chromatin structure and transcr... | ACCEPT | Summary: PARP1 binds nucleosomes specifically and compacts chromatin; nucleosomal histones are major substrates of PARP1/HPF1. Reason: Direct nucleosome-binding assays support this; nucleosome binding underlies PARP1 chromatin functions and histone serine ADP-ribosylation. Supporting Evidence: PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. PMID:15607977 Herein, we describe previously uncharacterized nucleosome binding properties of PARP-1 that promote the formation of compact, transcriptionally repressed chromatin structures. |
| GO:0031491 nucleosome binding | IDA PMID:31848352 PARP1 exhibits enhanced association and catalytic efficiency... | ACCEPT | Summary: PARP1 binds nucleosomes specifically and compacts chromatin; nucleosomal histones are major substrates of PARP1/HPF1. Reason: Direct nucleosome-binding assays support this; nucleosome binding underlies PARP1 chromatin functions and histone serine ADP-ribosylation. Supporting Evidence: PMID:31848352 This suggests that the Ξ³H2A.X epigenetic marker directly facilitates DNA repair by stabilizing PARP1 association and promoting catalysis. PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. |
| GO:0031491 nucleosome binding | IEA GO_REF:0000117 | ACCEPT | Summary: PARP1 binds nucleosomes specifically and compacts chromatin; nucleosomal histones are major substrates of PARP1/HPF1. Reason: Direct nucleosome-binding assays support this; nucleosome binding underlies PARP1 chromatin functions and histone serine ADP-ribosylation. Supporting Evidence: PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. |
| GO:0031625 ubiquitin protein ligase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: PARP1 binds ubiquitin ligases (e.g. RNF146, CHFR, RNF4-pathway factors) that act on PARylated or trapped PARP1. Reason: Ortholog projection consistent with known interactions with E3 ligases; non-core binding function. Supporting Evidence: PMID:35013556 We found that following trapping, PARP1 is SUMOylated by PIAS4 and subsequently ubiquitylated by the SUMO-targeted E3 ubiquitin ligase RNF4, events that promote recruitment of p97 and removal of trapped PARP1 from chromatin. |
| GO:0032042 mitochondrial DNA metabolic process | IMP PMID:25378300 Opposing roles of mitochondrial and nuclear PARP1 in the reg... | KEEP AS NON CORE | Summary: PARP1 depletion affects mitochondrial DNA metabolism. Reason: Non-core; from the same contested mitochondrial PARP1 study. Supporting Evidence: PMID:25378300 Our data show that intra-mitochondrial PARP1 interacts with a key mitochondrial-specific DNA base excision repair (BER) enzymes, namely EXOG and DNA polymerase gamma (PolΞ³), which under oxidative stress become poly(ADP-ribose)lated (PARylated). PMID:25378300 In summary, we conclude that mitochondrial PARP1, in opposite to nuclear PARP1, exerts a negative effect on several mitochondrial-specific transactions including the repair of the mitochondrial DNA. |
| GO:0032786 positive regulation of DNA-templated transcription, elongation | IDA PMID:27256882 Chemical genetic discovery of PARP targets reveals a role fo... | KEEP AS NON CORE | Summary: PARP1 ADP-ribosylates NELF-E, relieving promoter-proximal pausing and promoting elongation. Reason: Experimentally supported; non-core. Supporting Evidence: PMID:27256882 We found that PARP-1 ADP-ribosylates and inhibits negative elongation factor (NELF), a protein complex that regulates promoter-proximal pausing by RNA polymerase II (Pol II). PMID:27256882 Using this approach, we mapped hundreds of sites of ADP-ribosylation for PARPs 1, 2, and 3 across the proteome, as well as thousands of PARP-1-mediated ADP-ribosylation sites across the genome. |
| GO:0032869 cellular response to insulin stimulus | IDA PMID:19303849 A role of DNA-PK for the metabolic gene regulation in respon... | KEEP AS NON CORE | Summary: PARP1 is recruited with transcription factors to the FAS promoter in response to feeding/insulin. Reason: Context-specific; non-core. Supporting Evidence: PMID:19303849 Upon feeding, HDAC9 was no longer bound to the promoter, but the FAS promoter was now occupied by the coactivator P/CAF, DNA break/repair components that include DNA-PK, Ku70/80, PARP-1, TopoIIΞ², as well as PP1 (Fig. 1C, left panel). |
| GO:0032880 regulation of protein localization | IMP PMID:24550317 PARP1-dependent recruitment of KDM4D histone demethylase to ... | KEEP AS NON CORE | Summary: PARP1 activity regulates recruitment of other proteins to DNA damage sites. Reason: Non-core. Supporting Evidence: PMID:24550317 Interestingly, this recruitment is independent of the DDR sensor ataxia telangiectasia mutated (ATM), but dependent on poly (ADP-ribose) polymerase 1 (PARP1), which ADP ribosylates KDM4D after damage. |
| GO:0032991 protein-containing complex | IDA PMID:22504299 Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-Ξ³... | KEEP AS NON CORE | Summary: PARP1 is part of several protein complexes (e.g. with TrpRS and DNA-PKcs; with mitochondrial factors). Reason: Generic complex term; non-core. Supporting Evidence: PMID:22504299 Here we report a nuclear complex of TrpRS with the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) and with poly(ADP-ribose) polymerase 1 (PARP-1), the major PARP in human cells. |
| GO:0032991 protein-containing complex | IDA PMID:25378300 Opposing roles of mitochondrial and nuclear PARP1 in the reg... | KEEP AS NON CORE | Summary: PARP1 is part of several protein complexes (e.g. with TrpRS and DNA-PKcs; with mitochondrial factors). Reason: Generic complex term; non-core. Supporting Evidence: PMID:25378300 Our data show that intra-mitochondrial PARP1 interacts with a key mitochondrial-specific DNA base excision repair (BER) enzymes, namely EXOG and DNA polymerase gamma (PolΞ³), which under oxidative stress become poly(ADP-ribose)lated (PARylated). PMID:25378300 In summary, we conclude that mitochondrial PARP1, in opposite to nuclear PARP1, exerts a negative effect on several mitochondrial-specific transactions including the repair of the mitochondrial DNA. PMID:22504299 Here we report a nuclear complex of TrpRS with the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) and with poly(ADP-ribose) polymerase 1 (PARP-1), the major PARP in human cells. |
| GO:0032993 protein-DNA complex | IDA PMID:22504299 Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-Ξ³... | KEEP AS NON CORE | Summary: PARP1 is part of nuclear protein-DNA complexes (e.g. TrpRS-DNA-PKcs-PARP1). Reason: Correct but uninformative; non-core. Supporting Evidence: PMID:22504299 Here we report a nuclear complex of TrpRS with the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) and with poly(ADP-ribose) polymerase 1 (PARP-1), the major PARP in human cells. |
| GO:0033148 positive regulation of intracellular estrogen receptor signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog projection: PARP1 coactivates estrogen receptor-dependent signalling. Reason: Non-core. |
| GO:0034244 negative regulation of transcription elongation by RNA polymerase II | IDA PMID:35393539 Poly(ADP-ribosylation) of P-TEFb by PARP1 disrupts phase sep... | KEEP AS NON CORE | Summary: After DNA damage, PARP1 ADP-ribosylates cyclin T1, inactivating P-TEFb and inhibiting Pol II elongation. Reason: Experimentally supported; non-core. Supporting Evidence: PMID:35393539 Here we report that PARP1 inhibits Pol II elongation by inactivating the transcription elongation factor P-TEFb, a CDK9-cyclin T1 (CycT1) heterodimer. PMID:35393539 After sensing damage, the activated PARP1 binds to transcriptionally engaged P-TEFb and modifies CycT1 at multiple positions, including histidine residues that are rarely used as an acceptor site. |
| GO:0034599 cellular response to oxidative stress | IMP PMID:25378300 Opposing roles of mitochondrial and nuclear PARP1 in the reg... | KEEP AS NON CORE | Summary: PARP1 is activated by oxidative DNA damage and influences cell responses to oxidative stress. Reason: Response to oxidative DNA damage is a consequence of PARP1 damage sensing; non-core. Supporting Evidence: PMID:25378300 Our data show that intra-mitochondrial PARP1 interacts with a key mitochondrial-specific DNA base excision repair (BER) enzymes, namely EXOG and DNA polymerase gamma (PolΞ³), which under oxidative stress become poly(ADP-ribose)lated (PARylated). PMID:25378300 In summary, we conclude that mitochondrial PARP1, in opposite to nuclear PARP1, exerts a negative effect on several mitochondrial-specific transactions including the repair of the mitochondrial DNA. |
| GO:0034644 cellular response to UV | IMP PMID:24289924 Phosphorylation of p53 by TAF1 inactivates p53-dependent tra... | KEEP AS NON CORE | Summary: PARP1 is activated after UV damage and drives ATP depletion. Reason: Non-core response. Supporting Evidence: PMID:24289924 Upon DNA damage, cells undergo PARP-1-dependent ATP depletion, which is correlated with reduced TAF1 kinase activity and Thr55 phosphorylation, resulting in p21 activation. |
| GO:0035861 site of double-strand break | IDA PMID:26344098 Timeless Interacts with PARP-1 to Promote Homologous Recombi... | ACCEPT | Summary: PARP1 accumulates at DNA double-strand breaks. Reason: Supported by recruitment studies at DSBs; accepted. Supporting Evidence: PMID:26344098 We demonstrate that rapid and transient accumulation of Timeless at laser-induced DNA damage sites requires PARP-1, but not poly(ADP-ribosyl)ation and that Timeless is co-trapped with PARP-1 at DNA lesions upon PARP inhibition. PMID:30356214 In the nucleus, cGAS is recruited to double-stranded breaks and interacts with PARP1 via poly(ADP-ribose). |
| GO:0035861 site of double-strand break | IDA PMID:27568560 JNK Phosphorylates SIRT6 to Stimulate DNA Double-Strand Brea... | ACCEPT | Summary: PARP1 accumulates at DNA double-strand breaks. Reason: Supported by recruitment studies at DSBs; accepted. Supporting Evidence: PMID:27568560 This post-translational modification facilitates the mobilization of SIRT6 to DNA damage sites and is required for efficient recruitment of poly (ADP-ribose) polymerase 1 (PARP1) to DNA break sites and for efficient repair of DSBs. PMID:26344098 We demonstrate that rapid and transient accumulation of Timeless at laser-induced DNA damage sites requires PARP-1, but not poly(ADP-ribosyl)ation and that Timeless is co-trapped with PARP-1 at DNA lesions upon PARP inhibition. PMID:30356214 In the nucleus, cGAS is recruited to double-stranded breaks and interacts with PARP1 via poly(ADP-ribose). |
| GO:0035861 site of double-strand break | IDA PMID:29234005 Proteomic analyses identify ARH3 as a serine mono-ADP-ribosy... | ACCEPT | Summary: PARP1 accumulates at DNA double-strand breaks. Reason: Supported by recruitment studies at DSBs; accepted. Supporting Evidence: PMID:29234005 ARH3, but not PARG, efficiently demodified ARTD1-transmodified H3 histone tails, suggesting that ARH3 not only degrades ARTD1-mediated PARylation but also might be a mono-ADP-ribosylhydrolase (Supplementary Fig. 1b, c). PMID:26344098 We demonstrate that rapid and transient accumulation of Timeless at laser-induced DNA damage sites requires PARP-1, but not poly(ADP-ribosyl)ation and that Timeless is co-trapped with PARP-1 at DNA lesions upon PARP inhibition. PMID:30356214 In the nucleus, cGAS is recruited to double-stranded breaks and interacts with PARP1 via poly(ADP-ribose). |
| GO:0035861 site of double-strand break | IDA PMID:30356214 Nuclear cGAS suppresses DNA repair and promotes tumorigenesi... | ACCEPT | Summary: PARP1 accumulates at DNA double-strand breaks. Reason: Supported by recruitment studies at DSBs; accepted. Supporting Evidence: PMID:30356214 In the nucleus, cGAS is recruited to double-stranded breaks and interacts with PARP1 via poly(ADP-ribose). PMID:30356214 The cGAS-PARP1 interaction impedes the formation of the PARP1-Timeless complex, and thereby suppresses homologous recombination. PMID:26344098 We demonstrate that rapid and transient accumulation of Timeless at laser-induced DNA damage sites requires PARP-1, but not poly(ADP-ribosyl)ation and that Timeless is co-trapped with PARP-1 at DNA lesions upon PARP inhibition. |
| GO:0036211 protein modification process | IMP PMID:25378300 Opposing roles of mitochondrial and nuclear PARP1 in the reg... | ACCEPT | Summary: PARP1 modifies proteins post-translationally by ADP-ribosylation. Reason: General but correct process term for ADP-ribosylation of proteins by PARP1. Supporting Evidence: PMID:25378300 Our data show that intra-mitochondrial PARP1 interacts with a key mitochondrial-specific DNA base excision repair (BER) enzymes, namely EXOG and DNA polymerase gamma (PolΞ³), which under oxidative stress become poly(ADP-ribose)lated (PARylated). PMID:25378300 In summary, we conclude that mitochondrial PARP1, in opposite to nuclear PARP1, exerts a negative effect on several mitochondrial-specific transactions including the repair of the mitochondrial DNA. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. |
| GO:0042802 identical protein binding | IPI PMID:14734561 Identification and biochemical characterization of a Werner'... | KEEP AS NON CORE | Summary: PARP1 self-association was reported in interaction studies. Reason: PARP1 can multimerise on DNA and self-associates in some assays, but identical protein binding conveys little functional information. Kept as non-core rather than removed because the interaction evidence is experimental. |
| GO:0042802 identical protein binding | IPI PMID:23481255 Deficiency of terminal ADP-ribose protein glycohydrolase TAR... | KEEP AS NON CORE | Summary: PARP1 self-association was reported in interaction studies. Reason: PARP1 can multimerise on DNA and self-associates in some assays, but identical protein binding conveys little functional information. Kept as non-core rather than removed because the interaction evidence is experimental. |
| GO:0042803 protein homodimerization activity | IDA PMID:22683995 The zinc-finger domains of PARP1 cooperate to recognize DNA ... | KEEP AS NON CORE | Summary: PARP1 homodimerization was reported in studies of DNA damage-dependent activation. Reason: Older models proposed DNA-dependent dimerization of PARP1; current structural work favours a monomeric, intramolecular domain assembly on DNA breaks. Kept as non-core given the experimental support but contested mechanism. Supporting Evidence: PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. PMID:22683995 Upon activation at sites of DNA damage, PARP1 modifies itself and other proteins by covalent addition of long, branched polymers of ADP-ribose, which in turn recruit downstream DNA repair and chromatin remodeling factors. |
| GO:0042826 histone deacetylase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: PARP1 binds histone deacetylases in transcriptional complexes. Reason: Ortholog-projected binding consistent with PARP1 roles in transcription complexes; non-core. Supporting Evidence: PMID:19303849 Upon feeding, HDAC9 was no longer bound to the promoter, but the FAS promoter was now occupied by the coactivator P/CAF, DNA break/repair components that include DNA-PK, Ku70/80, PARP-1, TopoIIΞ², as well as PP1 (Fig. 1C, left panel). |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IDA PMID:22464733 Inflammasome-activated caspase 7 cleaves PARP1 to enhance th... | KEEP AS NON CORE | Summary: PARP1 regulates NF-kappaB target gene expression; its cleavage by caspase-7 derepresses targets. Reason: Non-core; PARP1 acts as a cofactor at NF-kappaB target promoters. Supporting Evidence: PMID:22464733 Here we show that after LPS stimulation, caspase 7 is activated by caspase 1, translocates to the nucleus, and cleaves PARP1 at the promoters of a subset of NF-ΞΊB target genes negatively regulated by PARP1. |
| GO:0043504 mitochondrial DNA repair | IMP PMID:25378300 Opposing roles of mitochondrial and nuclear PARP1 in the reg... | KEEP AS NON CORE | Summary: Mitochondrial PARP1 interacts with mitochondrial DNA repair factors; its loss alters mtDNA repair. Reason: Note the study concludes mitochondrial PARP1 has a negative effect on mtDNA repair. Kept as non-core and contested. Supporting Evidence: PMID:25378300 Our data show that intra-mitochondrial PARP1 interacts with a key mitochondrial-specific DNA base excision repair (BER) enzymes, namely EXOG and DNA polymerase gamma (PolΞ³), which under oxidative stress become poly(ADP-ribose)lated (PARylated). PMID:25378300 In summary, we conclude that mitochondrial PARP1, in opposite to nuclear PARP1, exerts a negative effect on several mitochondrial-specific transactions including the repair of the mitochondrial DNA. |
| GO:0043596 nuclear replication fork | IDA PMID:33412112 CARM1 regulates replication fork speed and stress response b... | KEEP AS NON CORE | Summary: PARP1 is present and active at nuclear replication forks, where CARM1 stimulates its PARylation activity. Reason: Supported experimentally; relates to replication-stress roles. Non-core. Supporting Evidence: PMID:33412112 Mechanistically, CARM1 interacts with PARP1 and promotes PARylation at replication forks. PMID:33412112 Thus, by stimulating PARP1, CARM1 slows replication forks and promotes the use of fork reversal in the stress response, revealing that CARM1 and PARP1 function as a regulatory module at forks to control fork speed and the choice of stress response mechanisms. |
| GO:0044378 non-sequence-specific DNA binding, bending | IDA PMID:36323657 Structural dynamics of DNA strand break sensing by PARP-1 at... | ACCEPT | Summary: PARP1 bends/kinks DNA at single-strand breaks independent of sequence as part of break recognition. Reason: smFRET shows PARP1 zinc fingers convert SSB DNA into a highly kinked conformation; this describes a genuine aspect of the sensor function. Supporting Evidence: PMID:36323657 Quantitative smFRET and structural ensemble calculations reveal how PARP-1's N-terminal zinc fingers convert DNA SSBs from a largely unperturbed conformation, via an intermediate state into the highly kinked DNA conformation. PMID:36323657 Our data suggest an induced fit mechanism via a multi-domain assembly cascade that drives SSB sensing and stimulates an interplay with the scaffold protein XRCC1 orchestrating subsequent DNA repair events. |
| GO:0045188 regulation of circadian sleep/wake cycle, non-REM sleep | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Transferred by sequence similarity: regulation of non-REM sleep. Reason: Organism-level behavioural phenotype from a rodent study; over-annotation. |
| GO:0045471 response to ethanol | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog projection: response to ethanol. Reason: Rodent response phenotype; over-annotation. |
| GO:0045824 negative regulation of innate immune response | IDA PMID:35460603 Cytoplasmic PARP1 links the genome instability to the inhibi... | KEEP AS NON CORE | Summary: Cytoplasmic PARP1 PARylates cGAS and suppresses its DNA-binding, dampening innate immune signalling. Reason: Experimentally supported; non-core. Supporting Evidence: PMID:35460603 Activated DNA-PK phosphorylates PARP1 on Thr594, thus facilitating the cytoplasmic translocation of PARP1 to inhibit the antiviral immunity both in vitro and in vivo. PMID:35460603 Mechanistically, cytoplasmic PARP1 interacts with and directly PARylates cyclic GMP-AMP synthase (cGAS) on Asp191 to inhibit its DNA-binding ability. |
| GO:0045824 negative regulation of innate immune response | IMP PMID:32844745 PARP1 inhibitors trigger innate immunity via PARP1 trapping-... | KEEP AS NON CORE | Summary: Cytoplasmic PARP1 PARylates cGAS and suppresses its DNA-binding, dampening innate immune signalling. Reason: Experimentally supported; non-core. Supporting Evidence: PMID:32844745 We find that the presence of the PARP1 protein with uncompromised DNA-binding activities is required for PARPi-induced innate immune response. PMID:35460603 Activated DNA-PK phosphorylates PARP1 on Thr594, thus facilitating the cytoplasmic translocation of PARP1 to inhibit the antiviral immunity both in vitro and in vivo. |
| GO:0045892 negative regulation of DNA-templated transcription | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Transferred by sequence similarity: PARP1 negatively regulates transcription. Reason: Non-core transcription regulation. Supporting Evidence: PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:11112786 A role for poly(ADP-ribose) polymerase in the transcriptiona... | KEEP AS NON CORE | Summary: PARP1 coactivates transcription of some genes (e.g. CXCL1). Reason: Context-dependent coactivator role; non-core. Supporting Evidence: PMID:11112786 The data point to the possibility that PARP may be a coactivator of CXCL1 transcription. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: PARP1 coactivates transcription of some genes (e.g. CXCL1). Reason: Context-dependent coactivator role; non-core. Supporting Evidence: PMID:11112786 The data point to the possibility that PARP may be a coactivator of CXCL1 transcription. |
| GO:0046697 decidualization | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Transferred by sequence similarity: decidualization. Reason: Tissue physiology from rodent studies; over-annotation. |
| GO:0051287 NAD binding | IEA GO_REF:0000120 | ACCEPT | Summary: The catalytic domain of PARP1 binds NAD+, its ADP-ribose donor. Reason: Correct mechanistic consequence of the ART fold; NAD+ is the substrate of the core activity. Supporting Evidence: PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. |
| GO:0051901 positive regulation of mitochondrial depolarization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog projection: PARP1 activation promotes mitochondrial depolarization. Reason: Downstream consequence of PARP1 hyperactivation in parthanatos; non-core. Supporting Evidence: PMID:12114629 We show that PARP-1 activation is required for translocation of apoptosis-inducing factor (AIF) from the mitochondria to the nucleus and that AIF is necessary for PARP-1-dependent cell death. |
| GO:0060391 positive regulation of SMAD protein signal transduction | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog projection: positive regulation of SMAD signal transduction. Reason: The direction and generality of PARP1 effects on SMAD signalling are uncertain (PARylation of SMADs has been reported to attenuate SMAD-DNA binding); likely an over-annotation. |
| GO:0060545 positive regulation of necroptotic process | ISS GO_REF:0000024 | MODIFY | Summary: PARP1 hyperactivation produces PAR that signals AIF release from mitochondria, driving caspase-independent parthanatos. Reason: The PARP1 contribution to parthanatos is real (PAR synthesis is the death signal; AIF release and chromatinolysis are performed by AIFM1 and MIF), but necroptosis is the wrong parent. GO:0070266 necroptotic process is defined by RIPK1/RIPK3 activation and critical dependence on MLKL, and parthanatos requires neither. GO lists "parthanatos" only as a synonym of necroptotic process and notes that whether it is an independent modality is still debated. GO:0097300 programmed necrotic cell death is the better fit, since its usage note covers programmed necrotic death where RIPK1/RIPK3 involvement is not shown. This is a non-core role. PARP1 is selected for DNA repair, and parthanatos arises from its hyperactivation under severe genotoxic or excitotoxic stress, with no established developmental or homeostatic role, so it is regulated rather than programmed death in the NCCD sense. AIFM1's own GO:0060545 annotation is UNDECIDED in its review, so it offers no convention to follow. Proposed replacements: programmed necrotic cell death Supporting Evidence: PMID:12114629 We show that PARP-1 activation is required for translocation of apoptosis-inducing factor (AIF) from the mitochondria to the nucleus and that AIF is necessary for PARP-1-dependent cell death. PMID:17116882 Here, we identify poly(ADP-ribose) (PAR) polymer, a product of PARP-1 activity, as a previously uncharacterized cell death signal. PMID:21467298 We show that AIF is a high-affinity poly(ADP-ribose) (PAR)-binding protein and that PAR binding to AIF is required for parthanatos both in vitro and in vivo. |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IPI PMID:19303849 A role of DNA-PK for the metabolic gene regulation in respon... | KEEP AS NON CORE | Summary: PARP1 associates with transcription factors at promoters, e.g. at the FAS promoter during feeding. Reason: Experimental interaction in a transcriptional context; non-core. Supporting Evidence: PMID:19303849 Upon feeding, HDAC9 was no longer bound to the promoter, but the FAS promoter was now occupied by the coactivator P/CAF, DNA break/repair components that include DNA-PK, Ku70/80, PARP-1, TopoIIΞ², as well as PP1 (Fig. 1C, left panel). |
| GO:0070212 obsolete protein poly-ADP-ribosylation | IDA PMID:15674325 PARP-10, a novel Myc-interacting protein with poly(ADP-ribos... | MODIFY | Summary: PARP1 poly-ADP-ribosylates itself and other proteins. Reason: GO:0070212 protein poly-ADP-ribosylation is obsolete (QuickGO: obsoleted because it represents a molecular function; consider GO:0003950). The underlying observation is correct; replace with the MF NAD+ poly-ADP-ribosyltransferase activity. Proposed replacements: NAD+ poly-ADP-ribosyltransferase activity Supporting Evidence: PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. |
| GO:0070212 obsolete protein poly-ADP-ribosylation | IDA PMID:19470756 SIRT1 promotes cell survival under stress by deacetylation-d... | MODIFY | Summary: PARP1 poly-ADP-ribosylates itself and other proteins. Reason: GO:0070212 protein poly-ADP-ribosylation is obsolete (QuickGO: obsoleted because it represents a molecular function; consider GO:0003950). The underlying observation is correct; replace with the MF NAD+ poly-ADP-ribosyltransferase activity. Proposed replacements: NAD+ poly-ADP-ribosyltransferase activity Supporting Evidence: PMID:19470756 Here, we show that PARP1 is acetylated after stress of cardiomyocytes, resulting in the activation of PARP1, which is independent of DNA damage. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. |
| GO:0070212 obsolete protein poly-ADP-ribosylation | IDA PMID:25043379 Family-wide analysis of poly(ADP-ribose) polymerase activity... | MODIFY | Summary: PARP1 poly-ADP-ribosylates itself and other proteins. Reason: GO:0070212 protein poly-ADP-ribosylation is obsolete (QuickGO: obsoleted because it represents a molecular function; consider GO:0003950). The underlying observation is correct; replace with the MF NAD+ poly-ADP-ribosyltransferase activity. Proposed replacements: NAD+ poly-ADP-ribosyltransferase activity Supporting Evidence: PMID:25043379 Here we show that the majority of PARPs generate MAR, not PAR, and demonstrate that the H-Y-E motif is not the sole indicator of PARP activity. PMID:25043379 We identify automodification sites on seven PARPs, and demonstrate that MAR and PAR generating PARPs modify similar amino acids, suggesting that the sequence and structural constraints limiting PARPs to MAR synthesis do not limit their ability to modify canonical amino-acid targets. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. |
| GO:0070212 obsolete protein poly-ADP-ribosylation | IDA PMID:28190768 Serine ADP-Ribosylation Depends on HPF1. | MODIFY | Summary: PARP1 poly-ADP-ribosylates itself and other proteins. Reason: GO:0070212 protein poly-ADP-ribosylation is obsolete (QuickGO: obsoleted because it represents a molecular function; consider GO:0003950). The underlying observation is correct; replace with the MF NAD+ poly-ADP-ribosyltransferase activity. Proposed replacements: NAD+ poly-ADP-ribosyltransferase activity Supporting Evidence: PMID:28190768 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. PMID:28190768 Moreover, adding HPF1 to in vitro PARP-1/PARP-2 reactions is necessary and sufficient for serine-specific ADPr of histones and PARP-1 itself. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. |
| GO:0070212 obsolete protein poly-ADP-ribosylation | IDA PMID:33186521 An HPF1/PARP1-Based Chemical Biology Strategy for Exploring ... | MODIFY | Summary: PARP1 poly-ADP-ribosylates itself and other proteins. Reason: GO:0070212 protein poly-ADP-ribosylation is obsolete (QuickGO: obsoleted because it represents a molecular function; consider GO:0003950). The underlying observation is correct; replace with the MF NAD+ poly-ADP-ribosyltransferase activity. Proposed replacements: NAD+ poly-ADP-ribosyltransferase activity Supporting Evidence: PMID:33186521 An HPF1/PARP1-Based Chemical Biology Strategy for Exploring ADP-Ribosylation. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. |
| GO:0070213 obsolete protein auto-ADP-ribosylation | IDA PMID:15607977 NAD+-dependent modulation of chromatin structure and transcr... | MODIFY | Summary: PARP1 automodifies itself with ADP-ribose, which releases it from DNA. Reason: GO:0070213 protein auto-ADP-ribosylation is obsolete (QuickGO: represents a molecular function; consider GO:0003950 or GO:1990404). Replace with GO:0003950; PARP1 is its own major acceptor. Proposed replacements: NAD+ poly-ADP-ribosyltransferase activity Supporting Evidence: PMID:15607977 PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. PMID:15607977 Herein, we describe previously uncharacterized nucleosome binding properties of PARP-1 that promote the formation of compact, transcriptionally repressed chromatin structures. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. |
| GO:0070213 obsolete protein auto-ADP-ribosylation | IDA PMID:20388712 The Zn3 domain of human poly(ADP-ribose) polymerase-1 (PARP-... | MODIFY | Summary: PARP1 automodifies itself with ADP-ribose, which releases it from DNA. Reason: GO:0070213 protein auto-ADP-ribosylation is obsolete (QuickGO: represents a molecular function; consider GO:0003950 or GO:1990404). Replace with GO:0003950; PARP1 is its own major acceptor. Proposed replacements: NAD+ poly-ADP-ribosyltransferase activity Supporting Evidence: PMID:20388712 PARP-1 attaches ADP-ribose units to target proteins, including itself as a post-translational modification that can change the biochemical properties of target proteins and mediate recruitment of proteins to sites of poly(ADP-ribose) synthesis. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:34210965 Specifically, we identify three serine residues within PARP1 (499, 507, and 519) as key sites whose efficient HPF1-dependent modification counters PARP1 trapping and contributes to inhibitor tolerance. |
| GO:0070213 obsolete protein auto-ADP-ribosylation | IDA PMID:29234005 Proteomic analyses identify ARH3 as a serine mono-ADP-ribosy... | MODIFY | Summary: PARP1 automodifies itself with ADP-ribose, which releases it from DNA. Reason: GO:0070213 protein auto-ADP-ribosylation is obsolete (QuickGO: represents a molecular function; consider GO:0003950 or GO:1990404). Replace with GO:0003950; PARP1 is its own major acceptor. Proposed replacements: NAD+ poly-ADP-ribosyltransferase activity Supporting Evidence: PMID:29234005 ARH3, but not PARG, efficiently demodified ARTD1-transmodified H3 histone tails, suggesting that ARH3 not only degrades ARTD1-mediated PARylation but also might be a mono-ADP-ribosylhydrolase (Supplementary Fig. 1b, c). PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:34210965 Specifically, we identify three serine residues within PARP1 (499, 507, and 519) as key sites whose efficient HPF1-dependent modification counters PARP1 trapping and contributes to inhibitor tolerance. |
| GO:0070213 obsolete protein auto-ADP-ribosylation | IDA PMID:30675909 Increased PARP1-DNA binding due to autoPARylation inhibition... | MODIFY | Summary: PARP1 automodifies itself with ADP-ribose, which releases it from DNA. Reason: GO:0070213 protein auto-ADP-ribosylation is obsolete (QuickGO: represents a molecular function; consider GO:0003950 or GO:1990404). Replace with GO:0003950; PARP1 is its own major acceptor. Proposed replacements: NAD+ poly-ADP-ribosyltransferase activity Supporting Evidence: PMID:30675909 PARP1 inhibitors (PARPis) are used clinically during cancer therapy and are thought to exert their cytotoxicity through PARP1 polymerase inhibition and PARP1-DNA trapping. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:34210965 Specifically, we identify three serine residues within PARP1 (499, 507, and 519) as key sites whose efficient HPF1-dependent modification counters PARP1 trapping and contributes to inhibitor tolerance. |
| GO:0070213 obsolete protein auto-ADP-ribosylation | IDA PMID:32358582 Real-time monitoring of PARP1-dependent PARylation by ATR-FT... | MODIFY | Summary: PARP1 automodifies itself with ADP-ribose, which releases it from DNA. Reason: GO:0070213 protein auto-ADP-ribosylation is obsolete (QuickGO: represents a molecular function; consider GO:0003950 or GO:1990404). Replace with GO:0003950; PARP1 is its own major acceptor. Proposed replacements: NAD+ poly-ADP-ribosyltransferase activity Supporting Evidence: PMID:32358582 This includes PARP1 activation by binding to DNA strand break models, NAD+ substrate binding, PAR formation, and dissociation of automodified PARP1 from DNA. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:34210965 Specifically, we identify three serine residues within PARP1 (499, 507, and 519) as key sites whose efficient HPF1-dependent modification counters PARP1 trapping and contributes to inhibitor tolerance. |
| GO:0070213 obsolete protein auto-ADP-ribosylation | IDA PMID:34210965 Serine-linked PARP1 auto-modification controls PARP inhibito... | MODIFY | Summary: PARP1 automodifies itself with ADP-ribose, which releases it from DNA. Reason: GO:0070213 protein auto-ADP-ribosylation is obsolete (QuickGO: represents a molecular function; consider GO:0003950 or GO:1990404). Replace with GO:0003950; PARP1 is its own major acceptor. Proposed replacements: NAD+ poly-ADP-ribosyltransferase activity Supporting Evidence: PMID:34210965 Specifically, we identify three serine residues within PARP1 (499, 507, and 519) as key sites whose efficient HPF1-dependent modification counters PARP1 trapping and contributes to inhibitor tolerance. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. |
| GO:0070213 obsolete protein auto-ADP-ribosylation | IDA PMID:34625544 The regulatory landscape of the human HPF1- and ARH3-depende... | MODIFY | Summary: PARP1 automodifies itself with ADP-ribose, which releases it from DNA. Reason: GO:0070213 protein auto-ADP-ribosylation is obsolete (QuickGO: represents a molecular function; consider GO:0003950 or GO:1990404). Replace with GO:0003950; PARP1 is its own major acceptor. Proposed replacements: NAD+ poly-ADP-ribosyltransferase activity Supporting Evidence: PMID:34625544 Our data support the notion that serine ADP-ribosylation mainly exists as mono-ADP-ribosylation in cells, and reveal a remarkable degree of histone co-modification with serine ADP-ribosylation and other post-translational modifications. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:34210965 Specifically, we identify three serine residues within PARP1 (499, 507, and 519) as key sites whose efficient HPF1-dependent modification counters PARP1 trapping and contributes to inhibitor tolerance. |
| GO:0070412 R-SMAD binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: PARP1 binds and ADP-ribosylates receptor-regulated SMADs (Smad3/Smad4). Reason: Ortholog-projected binding; PARP1-SMAD interaction modulates TGF-beta transcriptional responses. Non-core. |
| GO:0071168 protein localization to chromatin | IDA PMID:34874266 Serine ADP-ribosylation marks nucleosomes for ALC1-dependent... | KEEP AS NON CORE | Summary: PARP1/HPF1 histone serine ADP-ribosylation recruits chromatin remodelers such as ALC1 to damaged chromatin. Reason: Experimentally supported; non-core consequence of core activity. Supporting Evidence: PMID:34874266 Serine ADP-ribosylation (ADPr) is a DNA damage-induced post-translational modification catalyzed by the PARP1/2:HPF1 complex. PMID:34874266 This chemoenzymatic protein synthesis strategy was employed to assemble a series of full-length, ADP-ribosylated histones and show that ADPr at histone H2B serine 6 or histone H3 serine 10 converts nucleosomes into robust substrates for the chromatin remodeler ALC1. |
| GO:0071169 establishment of protein localization to chromatin | IDA PMID:36323657 Structural dynamics of DNA strand break sensing by PARP-1 at... | KEEP AS NON CORE | Summary: PARP1 binding to SSBs orchestrates recruitment of XRCC1 to chromatin. Reason: Non-core; part of SSB repair signalling. Supporting Evidence: PMID:36323657 Quantitative smFRET and structural ensemble calculations reveal how PARP-1's N-terminal zinc fingers convert DNA SSBs from a largely unperturbed conformation, via an intermediate state into the highly kinked DNA conformation. PMID:36323657 Our data suggest an induced fit mechanism via a multi-domain assembly cascade that drives SSB sensing and stimulates an interplay with the scaffold protein XRCC1 orchestrating subsequent DNA repair events. |
| GO:0071294 cellular response to zinc ion | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog projection: cellular response to zinc ion. Reason: Zinc is a structural cofactor of PARP1 zinc fingers; a response to zinc is not established. Over-annotation. |
| GO:0071560 cellular response to transforming growth factor beta stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog projection: cellular response to TGF-beta. Reason: Non-core. |
| GO:0071932 replication fork reversal | IDA PMID:33412112 CARM1 regulates replication fork speed and stress response b... | KEEP AS NON CORE | Summary: PARP1 activity, stimulated by CARM1, slows replication forks and promotes fork reversal. Reason: Experimentally supported role in replication stress; non-core. Supporting Evidence: PMID:33412112 Mechanistically, CARM1 interacts with PARP1 and promotes PARylation at replication forks. PMID:33412112 Thus, by stimulating PARP1, CARM1 slows replication forks and promotes the use of fork reversal in the stress response, revealing that CARM1 and PARP1 function as a regulatory module at forks to control fork speed and the choice of stress response mechanisms. |
| GO:0090734 site of DNA damage | IDA PMID:22683995 The zinc-finger domains of PARP1 cooperate to recognize DNA ... | ACCEPT | Summary: PARP1 is rapidly recruited to sites of DNA damage, where it is activated and synthesises PAR. Reason: Recruitment to laser microirradiation and other lesions is among the best documented PARP1 properties and reflects its core sensor role. Supporting Evidence: PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. PMID:22683995 Upon activation at sites of DNA damage, PARP1 modifies itself and other proteins by covalent addition of long, branched polymers of ADP-ribose, which in turn recruit downstream DNA repair and chromatin remodeling factors. PMID:30104678 Once DNA damage occurs, PARP1 is immediately recruited to the damaged DNA ends through its N-terminal DNA-binding motif, and stimulates PARylation via its C-terminal enzymatic domain20,21. |
| GO:0090734 site of DNA damage | IDA PMID:26626479 Structural Basis of Detection and Signaling of DNA Single-St... | ACCEPT | Summary: PARP1 is rapidly recruited to sites of DNA damage, where it is activated and synthesises PAR. Reason: Recruitment to laser microirradiation and other lesions is among the best documented PARP1 properties and reflects its core sensor role. Supporting Evidence: PMID:26626479 Poly(ADP-ribose)polymerase 1 (PARP-1) is a key eukaryotic stress sensor that responds in seconds to DNA single-strand breaks (SSBs), the most frequent genomic damage. PMID:26626479 Two flexibly linked N-terminal zinc fingers recognize the extreme deformability of SSBs and drive co-operative, stepwise self-assembly of remaining PARP-1 domains to control the activity of the C-terminal catalytic domain. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0090734 site of DNA damage | IDA PMID:26626480 PARP-1 Activation Requires Local Unfolding of an Autoinhibit... | ACCEPT | Summary: PARP1 is rapidly recruited to sites of DNA damage, where it is activated and synthesises PAR. Reason: Recruitment to laser microirradiation and other lesions is among the best documented PARP1 properties and reflects its core sensor role. Supporting Evidence: PMID:26626480 DNA breaks sharply elevate PARP-1 catalytic activity to mount a cell survival repair response, whereas persistent PARP-1 hyperactivation during severe genotoxic stress is associated with cell death. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. PMID:30104678 Once DNA damage occurs, PARP1 is immediately recruited to the damaged DNA ends through its N-terminal DNA-binding motif, and stimulates PARylation via its C-terminal enzymatic domain20,21. |
| GO:0090734 site of DNA damage | IDA PMID:30104678 PARP2 mediates branched poly ADP-ribosylation in response to... | ACCEPT | Summary: PARP1 is rapidly recruited to sites of DNA damage, where it is activated and synthesises PAR. Reason: Recruitment to laser microirradiation and other lesions is among the best documented PARP1 properties and reflects its core sensor role. Supporting Evidence: PMID:30104678 Once DNA damage occurs, PARP1 is immediately recruited to the damaged DNA ends through its N-terminal DNA-binding motif, and stimulates PARylation via its C-terminal enzymatic domain20,21. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0090734 site of DNA damage | IDA PMID:30675909 Increased PARP1-DNA binding due to autoPARylation inhibition... | ACCEPT | Summary: PARP1 is rapidly recruited to sites of DNA damage, where it is activated and synthesises PAR. Reason: Recruitment to laser microirradiation and other lesions is among the best documented PARP1 properties and reflects its core sensor role. Supporting Evidence: PMID:30675909 PARP1 inhibitors (PARPis) are used clinically during cancer therapy and are thought to exert their cytotoxicity through PARP1 polymerase inhibition and PARP1-DNA trapping. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. PMID:30104678 Once DNA damage occurs, PARP1 is immediately recruited to the damaged DNA ends through its N-terminal DNA-binding motif, and stimulates PARylation via its C-terminal enzymatic domain20,21. |
| GO:0090734 site of DNA damage | IDA PMID:31796734 Barrier-to-autointegration factor 1 (Banf1) regulates poly [... | ACCEPT | Summary: PARP1 is rapidly recruited to sites of DNA damage, where it is activated and synthesises PAR. Reason: Recruitment to laser microirradiation and other lesions is among the best documented PARP1 properties and reflects its core sensor role. Supporting Evidence: PMID:31796734 Specifically, oxidative lesions promote direct binding of Banf1 to PARP1, a critical NAD+-dependent DNA repair protein, leading to inhibition of PARP1 auto-ADP-ribosylation and defective repair of oxidative lesions, in cells with increased Banf1. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. PMID:30104678 Once DNA damage occurs, PARP1 is immediately recruited to the damaged DNA ends through its N-terminal DNA-binding motif, and stimulates PARylation via its C-terminal enzymatic domain20,21. |
| GO:0090734 site of DNA damage | IDA PMID:32028527 HPF1 completes the PARP active site for DNA damage-induced A... | ACCEPT | Summary: PARP1 is rapidly recruited to sites of DNA damage, where it is activated and synthesises PAR. Reason: Recruitment to laser microirradiation and other lesions is among the best documented PARP1 properties and reflects its core sensor role. Supporting Evidence: PMID:32028527 After binding to genomic lesions, these enzymes use NAD+ to modify numerous proteins with mono- and poly(ADP-ribose) signals that are important for the subsequent decompaction of chromatin and the recruitment of repair factors3,4. PMID:32028527 These post-translational modifications are predominantly serine-linked and require the accessory factor HPF1, which is specific for the DNA damage response and switches the amino acid specificity of PARP1 and PARP2 from aspartate or glutamate to serine residues5-10. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0090734 site of DNA damage | IDA PMID:32241924 Structural basis for allosteric PARP-1 retention on DNA brea... | ACCEPT | Summary: PARP1 is rapidly recruited to sites of DNA damage, where it is activated and synthesises PAR. Reason: Recruitment to laser microirradiation and other lesions is among the best documented PARP1 properties and reflects its core sensor role. Supporting Evidence: PMID:32241924 The success of poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors (PARPi) to treat cancer relates to their ability to trap PARP-1 at the site of a DNA break. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. PMID:30104678 Once DNA damage occurs, PARP1 is immediately recruited to the damaged DNA ends through its N-terminal DNA-binding motif, and stimulates PARylation via its C-terminal enzymatic domain20,21. |
| GO:0090734 site of DNA damage | IDA PMID:32358582 Real-time monitoring of PARP1-dependent PARylation by ATR-FT... | ACCEPT | Summary: PARP1 is rapidly recruited to sites of DNA damage, where it is activated and synthesises PAR. Reason: Recruitment to laser microirradiation and other lesions is among the best documented PARP1 properties and reflects its core sensor role. Supporting Evidence: PMID:32358582 This includes PARP1 activation by binding to DNA strand break models, NAD+ substrate binding, PAR formation, and dissociation of automodified PARP1 from DNA. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. PMID:30104678 Once DNA damage occurs, PARP1 is immediately recruited to the damaged DNA ends through its N-terminal DNA-binding motif, and stimulates PARylation via its C-terminal enzymatic domain20,21. |
| GO:0090734 site of DNA damage | IDA PMID:33186521 An HPF1/PARP1-Based Chemical Biology Strategy for Exploring ... | ACCEPT | Summary: PARP1 is rapidly recruited to sites of DNA damage, where it is activated and synthesises PAR. Reason: Recruitment to laser microirradiation and other lesions is among the best documented PARP1 properties and reflects its core sensor role. Supporting Evidence: PMID:33186521 An HPF1/PARP1-Based Chemical Biology Strategy for Exploring ADP-Ribosylation. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. PMID:30104678 Once DNA damage occurs, PARP1 is immediately recruited to the damaged DNA ends through its N-terminal DNA-binding motif, and stimulates PARylation via its C-terminal enzymatic domain20,21. |
| GO:0090734 site of DNA damage | IDA PMID:34795260 HPF1 dynamically controls the PARP1/2 balance between initia... | ACCEPT | Summary: PARP1 is rapidly recruited to sites of DNA damage, where it is activated and synthesises PAR. Reason: Recruitment to laser microirradiation and other lesions is among the best documented PARP1 properties and reflects its core sensor role. Supporting Evidence: PMID:34795260 HPF1 rapidly associates/dissociates from multiple PARP1 molecules, initiating serine modification before modification initiates on glutamate/aspartate, and accelerating initiation to be more comparable to elongation reactions forming poly(ADP-ribose). PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. PMID:30104678 Once DNA damage occurs, PARP1 is immediately recruited to the damaged DNA ends through its N-terminal DNA-binding motif, and stimulates PARylation via its C-terminal enzymatic domain20,21. |
| GO:0090734 site of DNA damage | IDA PMID:34874266 Serine ADP-ribosylation marks nucleosomes for ALC1-dependent... | ACCEPT | Summary: PARP1 is rapidly recruited to sites of DNA damage, where it is activated and synthesises PAR. Reason: Recruitment to laser microirradiation and other lesions is among the best documented PARP1 properties and reflects its core sensor role. Supporting Evidence: PMID:34874266 Serine ADP-ribosylation (ADPr) is a DNA damage-induced post-translational modification catalyzed by the PARP1/2:HPF1 complex. PMID:34874266 This chemoenzymatic protein synthesis strategy was employed to assemble a series of full-length, ADP-ribosylated histones and show that ADPr at histone H2B serine 6 or histone H3 serine 10 converts nucleosomes into robust substrates for the chromatin remodeler ALC1. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. |
| GO:0090734 site of DNA damage | IDA PMID:41062835 Stabilization of AFF1 by PARylation ensures transcriptional ... | ACCEPT | Summary: PARP1 is rapidly recruited to sites of DNA damage, where it is activated and synthesises PAR. Reason: Recruitment to laser microirradiation and other lesions is among the best documented PARP1 properties and reflects its core sensor role. Supporting Evidence: PMID:41062835 Upon DNA damage, PARP1 binds to and PARylates AFF1 in a region targeted by the E3 ligase Siah1, preventing AFF1 ubiquitination and promoting its stability. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. PMID:30104678 Once DNA damage occurs, PARP1 is immediately recruited to the damaged DNA ends through its N-terminal DNA-binding motif, and stimulates PARylation via its C-terminal enzymatic domain20,21. |
| GO:0090734 site of DNA damage | IEA GO_REF:0000117 | ACCEPT | Summary: PARP1 is rapidly recruited to sites of DNA damage, where it is activated and synthesises PAR. Reason: Recruitment to laser microirradiation and other lesions is among the best documented PARP1 properties and reflects its core sensor role. Supporting Evidence: PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. PMID:30104678 Once DNA damage occurs, PARP1 is immediately recruited to the damaged DNA ends through its N-terminal DNA-binding motif, and stimulates PARylation via its C-terminal enzymatic domain20,21. |
| GO:0090734 site of DNA damage | IMP PMID:27248496 WDR76 Co-Localizes with Heterochromatin Related Proteins and... | ACCEPT | Summary: PARP1 is rapidly recruited to sites of DNA damage, where it is activated and synthesises PAR. Reason: Recruitment to laser microirradiation and other lesions is among the best documented PARP1 properties and reflects its core sensor role. Supporting Evidence: PMID:27248496 Next, quantitative imaging studies demonstrated that WDR76 was recruited to laser induced DNA damage immediately after induction, and we compared the recruitment of WDR76 to laser induced DNA damage to known DNA damage proteins like PARP1, XRCC5, and RPA1. PMID:22683995 Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. PMID:30104678 Once DNA damage occurs, PARP1 is immediately recruited to the damaged DNA ends through its N-terminal DNA-binding motif, and stimulates PARylation via its C-terminal enzymatic domain20,21. |
| GO:0140294 NAD DNA ADP-ribosyltransferase activity | IDA PMID:27471034 Poly(ADP-ribose) polymerases covalently modify strand break ... | KEEP AS NON CORE | Summary: In vitro, PARP1 can attach ADP-ribose to phosphorylated DNA strand-break termini. Reason: DNA-end ADP-ribosylation by PARP1 is shown with purified enzyme and oligonucleotide substrates; the physiological significance in human cells is not established. Kept as non-core. Supporting Evidence: PMID:27471034 Here, in in vitro biochemical experiments, we found that the mammalian PARP1 and PARP2 proteins can directly ADP-ribosylate the termini of DNA oligonucleotides. PMID:27471034 PARP1 preferentially catalysed covalent attachment of ADP-ribose units to the ends of recessed DNA duplexes containing 3'-cordycepin, 5'- and 3'-phosphate and also to 5'-phosphate of a single-stranded oligonucleotide. |
| GO:0140294 NAD DNA ADP-ribosyltransferase activity | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: In vitro, PARP1 can attach ADP-ribose to phosphorylated DNA strand-break termini. Reason: DNA-end ADP-ribosylation by PARP1 is shown with purified enzyme and oligonucleotide substrates; the physiological significance in human cells is not established. Kept as non-core. Supporting Evidence: PMID:27471034 Here, in in vitro biochemical experiments, we found that the mammalian PARP1 and PARP2 proteins can directly ADP-ribosylate the termini of DNA oligonucleotides. |
| GO:0140537 transcription regulator activator activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: PARP1 acts as a transcriptional coactivator for some transcription factors (e.g. NF-kappaB targets). Reason: Ortholog projection consistent with coactivator roles; non-core. Supporting Evidence: PMID:11112786 The data point to the possibility that PARP may be a coactivator of CXCL1 transcription. |
| GO:0140805 NAD+-protein-serine ADP-ribosyltransferase activity | EXP PMID:27067600 HPF1/C4orf27 Is a PARP-1-Interacting Protein that Regulates ... | ACCEPT | Summary: Together with its accessory factor HPF1, PARP1 transfers ADP-ribose to serine residues of histones and of PARP1 itself; serine is the major ADP-ribosylation acceptor after DNA damage. Reason: Serine ADP-ribosylation by the PARP1/HPF1 complex is the predominant DNA damage-induced modification in cells and is directly demonstrated in vitro with purified proteins and by proteomics. Core activity; it requires HPF1 (HPF1 supplies the catalytic base Glu284 in the shared active site) but PARP1 provides the NAD+-binding catalytic domain. Supporting Evidence: PMID:27067600 Functionally, HPF1 promotes PARP-1-dependent in trans ADP-ribosylation of histones and limits DNA damage-induced hyper-automodification of PARP-1. PMID:28190768 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. PMID:32028527 After binding to genomic lesions, these enzymes use NAD+ to modify numerous proteins with mono- and poly(ADP-ribose) signals that are important for the subsequent decompaction of chromatin and the recruitment of repair factors3,4. |
| GO:0140805 NAD+-protein-serine ADP-ribosyltransferase activity | EXP PMID:27256882 Chemical genetic discovery of PARP targets reveals a role fo... | ACCEPT | Summary: Together with its accessory factor HPF1, PARP1 transfers ADP-ribose to serine residues of histones and of PARP1 itself; serine is the major ADP-ribosylation acceptor after DNA damage. Reason: Serine ADP-ribosylation by the PARP1/HPF1 complex is the predominant DNA damage-induced modification in cells and is directly demonstrated in vitro with purified proteins and by proteomics. Core activity; it requires HPF1 (HPF1 supplies the catalytic base Glu284 in the shared active site) but PARP1 provides the NAD+-binding catalytic domain. Supporting Evidence: PMID:27256882 We found that PARP-1 ADP-ribosylates and inhibits negative elongation factor (NELF), a protein complex that regulates promoter-proximal pausing by RNA polymerase II (Pol II). PMID:27256882 Using this approach, we mapped hundreds of sites of ADP-ribosylation for PARPs 1, 2, and 3 across the proteome, as well as thousands of PARP-1-mediated ADP-ribosylation sites across the genome. PMID:28190768 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. |
| GO:0140805 NAD+-protein-serine ADP-ribosyltransferase activity | EXP PMID:34625544 The regulatory landscape of the human HPF1- and ARH3-depende... | ACCEPT | Summary: Together with its accessory factor HPF1, PARP1 transfers ADP-ribose to serine residues of histones and of PARP1 itself; serine is the major ADP-ribosylation acceptor after DNA damage. Reason: Serine ADP-ribosylation by the PARP1/HPF1 complex is the predominant DNA damage-induced modification in cells and is directly demonstrated in vitro with purified proteins and by proteomics. Core activity; it requires HPF1 (HPF1 supplies the catalytic base Glu284 in the shared active site) but PARP1 provides the NAD+-binding catalytic domain. Supporting Evidence: PMID:34625544 Our data support the notion that serine ADP-ribosylation mainly exists as mono-ADP-ribosylation in cells, and reveal a remarkable degree of histone co-modification with serine ADP-ribosylation and other post-translational modifications. PMID:28190768 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. PMID:32028527 After binding to genomic lesions, these enzymes use NAD+ to modify numerous proteins with mono- and poly(ADP-ribose) signals that are important for the subsequent decompaction of chromatin and the recruitment of repair factors3,4. |
| GO:0140805 NAD+-protein-serine ADP-ribosyltransferase activity | IDA PMID:28190768 Serine ADP-Ribosylation Depends on HPF1. | ACCEPT | Summary: Together with its accessory factor HPF1, PARP1 transfers ADP-ribose to serine residues of histones and of PARP1 itself; serine is the major ADP-ribosylation acceptor after DNA damage. Reason: Serine ADP-ribosylation by the PARP1/HPF1 complex is the predominant DNA damage-induced modification in cells and is directly demonstrated in vitro with purified proteins and by proteomics. Core activity; it requires HPF1 (HPF1 supplies the catalytic base Glu284 in the shared active site) but PARP1 provides the NAD+-binding catalytic domain. Supporting Evidence: PMID:28190768 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. PMID:28190768 Moreover, adding HPF1 to in vitro PARP-1/PARP-2 reactions is necessary and sufficient for serine-specific ADPr of histones and PARP-1 itself. PMID:32028527 After binding to genomic lesions, these enzymes use NAD+ to modify numerous proteins with mono- and poly(ADP-ribose) signals that are important for the subsequent decompaction of chromatin and the recruitment of repair factors3,4. |
| GO:0140805 NAD+-protein-serine ADP-ribosyltransferase activity | IDA PMID:29234005 Proteomic analyses identify ARH3 as a serine mono-ADP-ribosy... | ACCEPT | Summary: Together with its accessory factor HPF1, PARP1 transfers ADP-ribose to serine residues of histones and of PARP1 itself; serine is the major ADP-ribosylation acceptor after DNA damage. Reason: Serine ADP-ribosylation by the PARP1/HPF1 complex is the predominant DNA damage-induced modification in cells and is directly demonstrated in vitro with purified proteins and by proteomics. Core activity; it requires HPF1 (HPF1 supplies the catalytic base Glu284 in the shared active site) but PARP1 provides the NAD+-binding catalytic domain. Supporting Evidence: PMID:29234005 ARH3, but not PARG, efficiently demodified ARTD1-transmodified H3 histone tails, suggesting that ARH3 not only degrades ARTD1-mediated PARylation but also might be a mono-ADP-ribosylhydrolase (Supplementary Fig. 1b, c). PMID:28190768 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. PMID:32028527 After binding to genomic lesions, these enzymes use NAD+ to modify numerous proteins with mono- and poly(ADP-ribose) signals that are important for the subsequent decompaction of chromatin and the recruitment of repair factors3,4. |
| GO:0140805 NAD+-protein-serine ADP-ribosyltransferase activity | IDA PMID:32028527 HPF1 completes the PARP active site for DNA damage-induced A... | ACCEPT | Summary: Together with its accessory factor HPF1, PARP1 transfers ADP-ribose to serine residues of histones and of PARP1 itself; serine is the major ADP-ribosylation acceptor after DNA damage. Reason: Serine ADP-ribosylation by the PARP1/HPF1 complex is the predominant DNA damage-induced modification in cells and is directly demonstrated in vitro with purified proteins and by proteomics. Core activity; it requires HPF1 (HPF1 supplies the catalytic base Glu284 in the shared active site) but PARP1 provides the NAD+-binding catalytic domain. Supporting Evidence: PMID:32028527 After binding to genomic lesions, these enzymes use NAD+ to modify numerous proteins with mono- and poly(ADP-ribose) signals that are important for the subsequent decompaction of chromatin and the recruitment of repair factors3,4. PMID:32028527 These post-translational modifications are predominantly serine-linked and require the accessory factor HPF1, which is specific for the DNA damage response and switches the amino acid specificity of PARP1 and PARP2 from aspartate or glutamate to serine residues5-10. PMID:28190768 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. |
| GO:0140805 NAD+-protein-serine ADP-ribosyltransferase activity | IDA PMID:33186521 An HPF1/PARP1-Based Chemical Biology Strategy for Exploring ... | ACCEPT | Summary: Together with its accessory factor HPF1, PARP1 transfers ADP-ribose to serine residues of histones and of PARP1 itself; serine is the major ADP-ribosylation acceptor after DNA damage. Reason: Serine ADP-ribosylation by the PARP1/HPF1 complex is the predominant DNA damage-induced modification in cells and is directly demonstrated in vitro with purified proteins and by proteomics. Core activity; it requires HPF1 (HPF1 supplies the catalytic base Glu284 in the shared active site) but PARP1 provides the NAD+-binding catalytic domain. Supporting Evidence: PMID:33186521 An HPF1/PARP1-Based Chemical Biology Strategy for Exploring ADP-Ribosylation. PMID:28190768 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. PMID:32028527 After binding to genomic lesions, these enzymes use NAD+ to modify numerous proteins with mono- and poly(ADP-ribose) signals that are important for the subsequent decompaction of chromatin and the recruitment of repair factors3,4. |
| GO:0140805 NAD+-protein-serine ADP-ribosyltransferase activity | IDA PMID:33412112 CARM1 regulates replication fork speed and stress response b... | ACCEPT | Summary: Together with its accessory factor HPF1, PARP1 transfers ADP-ribose to serine residues of histones and of PARP1 itself; serine is the major ADP-ribosylation acceptor after DNA damage. Reason: Serine ADP-ribosylation by the PARP1/HPF1 complex is the predominant DNA damage-induced modification in cells and is directly demonstrated in vitro with purified proteins and by proteomics. Core activity; it requires HPF1 (HPF1 supplies the catalytic base Glu284 in the shared active site) but PARP1 provides the NAD+-binding catalytic domain. Supporting Evidence: PMID:33412112 Mechanistically, CARM1 interacts with PARP1 and promotes PARylation at replication forks. PMID:33412112 Thus, by stimulating PARP1, CARM1 slows replication forks and promotes the use of fork reversal in the stress response, revealing that CARM1 and PARP1 function as a regulatory module at forks to control fork speed and the choice of stress response mechanisms. PMID:28190768 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. |
| GO:0140805 NAD+-protein-serine ADP-ribosyltransferase activity | IDA PMID:33589610 HPF1 remodels the active site of PARP1 to enable the serine ... | ACCEPT | Summary: Together with its accessory factor HPF1, PARP1 transfers ADP-ribose to serine residues of histones and of PARP1 itself; serine is the major ADP-ribosylation acceptor after DNA damage. Reason: Serine ADP-ribosylation by the PARP1/HPF1 complex is the predominant DNA damage-induced modification in cells and is directly demonstrated in vitro with purified proteins and by proteomics. Core activity; it requires HPF1 (HPF1 supplies the catalytic base Glu284 in the shared active site) but PARP1 provides the NAD+-binding catalytic domain. Supporting Evidence: PMID:33589610 Serine is the major residue for ADP-ribosylation upon DNA damage, which strictly depends on HPF1. PMID:28190768 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. PMID:32028527 After binding to genomic lesions, these enzymes use NAD+ to modify numerous proteins with mono- and poly(ADP-ribose) signals that are important for the subsequent decompaction of chromatin and the recruitment of repair factors3,4. |
| GO:0140805 NAD+-protein-serine ADP-ribosyltransferase activity | IDA PMID:33683197 HPF1 and nucleosomes mediate a dramatic switch in activity o... | ACCEPT | Summary: Together with its accessory factor HPF1, PARP1 transfers ADP-ribose to serine residues of histones and of PARP1 itself; serine is the major ADP-ribosylation acceptor after DNA damage. Reason: Serine ADP-ribosylation by the PARP1/HPF1 complex is the predominant DNA damage-induced modification in cells and is directly demonstrated in vitro with purified proteins and by proteomics. Core activity; it requires HPF1 (HPF1 supplies the catalytic base Glu284 in the shared active site) but PARP1 provides the NAD+-binding catalytic domain. Supporting Evidence: PMID:33683197 HPF1 provides that catalytic base Glu284 to substantially redirect PARylation by PARP1 such that the histones in nucleosomes become the primary recipients of PAR chains. PMID:28190768 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. PMID:32028527 After binding to genomic lesions, these enzymes use NAD+ to modify numerous proteins with mono- and poly(ADP-ribose) signals that are important for the subsequent decompaction of chromatin and the recruitment of repair factors3,4. |
| GO:0140805 NAD+-protein-serine ADP-ribosyltransferase activity | IDA PMID:34210965 Serine-linked PARP1 auto-modification controls PARP inhibito... | ACCEPT | Summary: Together with its accessory factor HPF1, PARP1 transfers ADP-ribose to serine residues of histones and of PARP1 itself; serine is the major ADP-ribosylation acceptor after DNA damage. Reason: Serine ADP-ribosylation by the PARP1/HPF1 complex is the predominant DNA damage-induced modification in cells and is directly demonstrated in vitro with purified proteins and by proteomics. Core activity; it requires HPF1 (HPF1 supplies the catalytic base Glu284 in the shared active site) but PARP1 provides the NAD+-binding catalytic domain. Supporting Evidence: PMID:34210965 Specifically, we identify three serine residues within PARP1 (499, 507, and 519) as key sites whose efficient HPF1-dependent modification counters PARP1 trapping and contributes to inhibitor tolerance. PMID:28190768 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. PMID:32028527 After binding to genomic lesions, these enzymes use NAD+ to modify numerous proteins with mono- and poly(ADP-ribose) signals that are important for the subsequent decompaction of chromatin and the recruitment of repair factors3,4. |
| GO:0140805 NAD+-protein-serine ADP-ribosyltransferase activity | IDA PMID:34732825 Dual function of HPF1 in the modulation of PARP1 and PARP2 a... | ACCEPT | Summary: Together with its accessory factor HPF1, PARP1 transfers ADP-ribose to serine residues of histones and of PARP1 itself; serine is the major ADP-ribosylation acceptor after DNA damage. Reason: Serine ADP-ribosylation by the PARP1/HPF1 complex is the predominant DNA damage-induced modification in cells and is directly demonstrated in vitro with purified proteins and by proteomics. Core activity; it requires HPF1 (HPF1 supplies the catalytic base Glu284 in the shared active site) but PARP1 provides the NAD+-binding catalytic domain. Supporting Evidence: PMID:34732825 Here we demonstrate that HPF1 can stimulate the DNA-dependent and DNA-independent autoPARylation of PARP1 and PARP2 as well as the heteroPARylation of histones in the complex with nucleosome. PMID:28190768 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. PMID:32028527 After binding to genomic lesions, these enzymes use NAD+ to modify numerous proteins with mono- and poly(ADP-ribose) signals that are important for the subsequent decompaction of chromatin and the recruitment of repair factors3,4. |
| GO:0140805 NAD+-protein-serine ADP-ribosyltransferase activity | IDA PMID:34795260 HPF1 dynamically controls the PARP1/2 balance between initia... | ACCEPT | Summary: Together with its accessory factor HPF1, PARP1 transfers ADP-ribose to serine residues of histones and of PARP1 itself; serine is the major ADP-ribosylation acceptor after DNA damage. Reason: Serine ADP-ribosylation by the PARP1/HPF1 complex is the predominant DNA damage-induced modification in cells and is directly demonstrated in vitro with purified proteins and by proteomics. Core activity; it requires HPF1 (HPF1 supplies the catalytic base Glu284 in the shared active site) but PARP1 provides the NAD+-binding catalytic domain. Supporting Evidence: PMID:34795260 HPF1 rapidly associates/dissociates from multiple PARP1 molecules, initiating serine modification before modification initiates on glutamate/aspartate, and accelerating initiation to be more comparable to elongation reactions forming poly(ADP-ribose). PMID:28190768 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. PMID:32028527 After binding to genomic lesions, these enzymes use NAD+ to modify numerous proteins with mono- and poly(ADP-ribose) signals that are important for the subsequent decompaction of chromatin and the recruitment of repair factors3,4. |
| GO:0140805 NAD+-protein-serine ADP-ribosyltransferase activity | IDA PMID:34874266 Serine ADP-ribosylation marks nucleosomes for ALC1-dependent... | ACCEPT | Summary: Together with its accessory factor HPF1, PARP1 transfers ADP-ribose to serine residues of histones and of PARP1 itself; serine is the major ADP-ribosylation acceptor after DNA damage. Reason: Serine ADP-ribosylation by the PARP1/HPF1 complex is the predominant DNA damage-induced modification in cells and is directly demonstrated in vitro with purified proteins and by proteomics. Core activity; it requires HPF1 (HPF1 supplies the catalytic base Glu284 in the shared active site) but PARP1 provides the NAD+-binding catalytic domain. Supporting Evidence: PMID:34874266 Serine ADP-ribosylation (ADPr) is a DNA damage-induced post-translational modification catalyzed by the PARP1/2:HPF1 complex. PMID:34874266 This chemoenzymatic protein synthesis strategy was employed to assemble a series of full-length, ADP-ribosylated histones and show that ADPr at histone H2B serine 6 or histone H3 serine 10 converts nucleosomes into robust substrates for the chromatin remodeler ALC1. PMID:28190768 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. |
| GO:0140805 NAD+-protein-serine ADP-ribosyltransferase activity | IDA PMID:35393539 Poly(ADP-ribosylation) of P-TEFb by PARP1 disrupts phase sep... | ACCEPT | Summary: Together with its accessory factor HPF1, PARP1 transfers ADP-ribose to serine residues of histones and of PARP1 itself; serine is the major ADP-ribosylation acceptor after DNA damage. Reason: Serine ADP-ribosylation by the PARP1/HPF1 complex is the predominant DNA damage-induced modification in cells and is directly demonstrated in vitro with purified proteins and by proteomics. Core activity; it requires HPF1 (HPF1 supplies the catalytic base Glu284 in the shared active site) but PARP1 provides the NAD+-binding catalytic domain. Supporting Evidence: PMID:35393539 Here we report that PARP1 inhibits Pol II elongation by inactivating the transcription elongation factor P-TEFb, a CDK9-cyclin T1 (CycT1) heterodimer. PMID:35393539 After sensing damage, the activated PARP1 binds to transcriptionally engaged P-TEFb and modifies CycT1 at multiple positions, including histidine residues that are rarely used as an acceptor site. PMID:28190768 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. |
| GO:0140805 NAD+-protein-serine ADP-ribosyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Together with its accessory factor HPF1, PARP1 transfers ADP-ribose to serine residues of histones and of PARP1 itself; serine is the major ADP-ribosylation acceptor after DNA damage. Reason: Serine ADP-ribosylation by the PARP1/HPF1 complex is the predominant DNA damage-induced modification in cells and is directly demonstrated in vitro with purified proteins and by proteomics. Core activity; it requires HPF1 (HPF1 supplies the catalytic base Glu284 in the shared active site) but PARP1 provides the NAD+-binding catalytic domain. Supporting Evidence: PMID:28190768 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. PMID:32028527 After binding to genomic lesions, these enzymes use NAD+ to modify numerous proteins with mono- and poly(ADP-ribose) signals that are important for the subsequent decompaction of chromatin and the recruitment of repair factors3,4. PMID:33589610 Serine is the major residue for ADP-ribosylation upon DNA damage, which strictly depends on HPF1. |
| GO:0140806 NAD+-protein-aspartate ADP-ribosyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: In the absence of HPF1, PARP1 ADP-ribosylates aspartate (and glutamate) residues, including in its automodification domain and on cGAS Asp191. Reason: Aspartate/glutamate modification by PARP1 alone is shown by mass spectrometric site mapping of the automodification domain and other substrates; supported by IBA. Accepted as part of the core ADP-ribosyltransferase activity, while noting that in cells HPF1 shifts much modification to serine. Supporting Evidence: PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:32028527 After binding to genomic lesions, these enzymes use NAD+ to modify numerous proteins with mono- and poly(ADP-ribose) signals that are important for the subsequent decompaction of chromatin and the recruitment of repair factors3,4. |
| GO:0140806 NAD+-protein-aspartate ADP-ribosyltransferase activity | IDA PMID:19764761 Identification of the ADP-ribosylation sites in the PARP-1 a... | ACCEPT | Summary: In the absence of HPF1, PARP1 ADP-ribosylates aspartate (and glutamate) residues, including in its automodification domain and on cGAS Asp191. Reason: Aspartate/glutamate modification by PARP1 alone is shown by mass spectrometric site mapping of the automodification domain and other substrates; supported by IBA. Accepted as part of the core ADP-ribosyltransferase activity, while noting that in cells HPF1 shifts much modification to serine. Supporting Evidence: PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:19764761 Here we report a strategy to identify the modification sites on domain D using the PARP-1 E988Q mutant, which only catalyzes mono(ADP-ribosyl)ation. PMID:32028527 After binding to genomic lesions, these enzymes use NAD+ to modify numerous proteins with mono- and poly(ADP-ribose) signals that are important for the subsequent decompaction of chromatin and the recruitment of repair factors3,4. |
| GO:0140806 NAD+-protein-aspartate ADP-ribosyltransferase activity | IDA PMID:25043379 Family-wide analysis of poly(ADP-ribose) polymerase activity... | ACCEPT | Summary: In the absence of HPF1, PARP1 ADP-ribosylates aspartate (and glutamate) residues, including in its automodification domain and on cGAS Asp191. Reason: Aspartate/glutamate modification by PARP1 alone is shown by mass spectrometric site mapping of the automodification domain and other substrates; supported by IBA. Accepted as part of the core ADP-ribosyltransferase activity, while noting that in cells HPF1 shifts much modification to serine. Supporting Evidence: PMID:25043379 Here we show that the majority of PARPs generate MAR, not PAR, and demonstrate that the H-Y-E motif is not the sole indicator of PARP activity. PMID:25043379 We identify automodification sites on seven PARPs, and demonstrate that MAR and PAR generating PARPs modify similar amino acids, suggesting that the sequence and structural constraints limiting PARPs to MAR synthesis do not limit their ability to modify canonical amino-acid targets. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. |
| GO:0140806 NAD+-protein-aspartate ADP-ribosyltransferase activity | IDA PMID:35460603 Cytoplasmic PARP1 links the genome instability to the inhibi... | ACCEPT | Summary: In the absence of HPF1, PARP1 ADP-ribosylates aspartate (and glutamate) residues, including in its automodification domain and on cGAS Asp191. Reason: Aspartate/glutamate modification by PARP1 alone is shown by mass spectrometric site mapping of the automodification domain and other substrates; supported by IBA. Accepted as part of the core ADP-ribosyltransferase activity, while noting that in cells HPF1 shifts much modification to serine. Supporting Evidence: PMID:35460603 Activated DNA-PK phosphorylates PARP1 on Thr594, thus facilitating the cytoplasmic translocation of PARP1 to inhibit the antiviral immunity both in vitro and in vivo. PMID:35460603 Mechanistically, cytoplasmic PARP1 interacts with and directly PARylates cyclic GMP-AMP synthase (cGAS) on Asp191 to inhibit its DNA-binding ability. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. |
| GO:0140806 NAD+-protein-aspartate ADP-ribosyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: In the absence of HPF1, PARP1 ADP-ribosylates aspartate (and glutamate) residues, including in its automodification domain and on cGAS Asp191. Reason: Aspartate/glutamate modification by PARP1 alone is shown by mass spectrometric site mapping of the automodification domain and other substrates; supported by IBA. Accepted as part of the core ADP-ribosyltransferase activity, while noting that in cells HPF1 shifts much modification to serine. Supporting Evidence: PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:32028527 After binding to genomic lesions, these enzymes use NAD+ to modify numerous proteins with mono- and poly(ADP-ribose) signals that are important for the subsequent decompaction of chromatin and the recruitment of repair factors3,4. |
| GO:0140807 NAD+-protein-glutamate ADP-ribosyltransferase activity | EXP PMID:25043379 Family-wide analysis of poly(ADP-ribose) polymerase activity... | ACCEPT | Summary: PARP1 ADP-ribosylates glutamate residues, e.g. in its automodification domain and on NELF-E. Reason: Glutamate-linked ADP-ribosylation by PARP1 is supported by direct site mapping (automodification domain, NELF-E) and IBA. Accepted as a facet of the core activity; HPF1 redirects specificity toward serine in the DNA damage response. Supporting Evidence: PMID:25043379 Here we show that the majority of PARPs generate MAR, not PAR, and demonstrate that the H-Y-E motif is not the sole indicator of PARP activity. PMID:25043379 We identify automodification sites on seven PARPs, and demonstrate that MAR and PAR generating PARPs modify similar amino acids, suggesting that the sequence and structural constraints limiting PARPs to MAR synthesis do not limit their ability to modify canonical amino-acid targets. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. |
| GO:0140807 NAD+-protein-glutamate ADP-ribosyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PARP1 ADP-ribosylates glutamate residues, e.g. in its automodification domain and on NELF-E. Reason: Glutamate-linked ADP-ribosylation by PARP1 is supported by direct site mapping (automodification domain, NELF-E) and IBA. Accepted as a facet of the core activity; HPF1 redirects specificity toward serine in the DNA damage response. Supporting Evidence: PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:32028527 After binding to genomic lesions, these enzymes use NAD+ to modify numerous proteins with mono- and poly(ADP-ribose) signals that are important for the subsequent decompaction of chromatin and the recruitment of repair factors3,4. |
| GO:0140807 NAD+-protein-glutamate ADP-ribosyltransferase activity | IDA PMID:19764761 Identification of the ADP-ribosylation sites in the PARP-1 a... | ACCEPT | Summary: PARP1 ADP-ribosylates glutamate residues, e.g. in its automodification domain and on NELF-E. Reason: Glutamate-linked ADP-ribosylation by PARP1 is supported by direct site mapping (automodification domain, NELF-E) and IBA. Accepted as a facet of the core activity; HPF1 redirects specificity toward serine in the DNA damage response. Supporting Evidence: PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:19764761 Here we report a strategy to identify the modification sites on domain D using the PARP-1 E988Q mutant, which only catalyzes mono(ADP-ribosyl)ation. PMID:32028527 After binding to genomic lesions, these enzymes use NAD+ to modify numerous proteins with mono- and poly(ADP-ribose) signals that are important for the subsequent decompaction of chromatin and the recruitment of repair factors3,4. |
| GO:0140807 NAD+-protein-glutamate ADP-ribosyltransferase activity | IDA PMID:27256882 Chemical genetic discovery of PARP targets reveals a role fo... | ACCEPT | Summary: PARP1 ADP-ribosylates glutamate residues, e.g. in its automodification domain and on NELF-E. Reason: Glutamate-linked ADP-ribosylation by PARP1 is supported by direct site mapping (automodification domain, NELF-E) and IBA. Accepted as a facet of the core activity; HPF1 redirects specificity toward serine in the DNA damage response. Supporting Evidence: PMID:27256882 We found that PARP-1 ADP-ribosylates and inhibits negative elongation factor (NELF), a protein complex that regulates promoter-proximal pausing by RNA polymerase II (Pol II). PMID:27256882 Using this approach, we mapped hundreds of sites of ADP-ribosylation for PARPs 1, 2, and 3 across the proteome, as well as thousands of PARP-1-mediated ADP-ribosylation sites across the genome. PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. |
| GO:0140807 NAD+-protein-glutamate ADP-ribosyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: PARP1 ADP-ribosylates glutamate residues, e.g. in its automodification domain and on NELF-E. Reason: Glutamate-linked ADP-ribosylation by PARP1 is supported by direct site mapping (automodification domain, NELF-E) and IBA. Accepted as a facet of the core activity; HPF1 redirects specificity toward serine in the DNA damage response. Supporting Evidence: PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:32028527 After binding to genomic lesions, these enzymes use NAD+ to modify numerous proteins with mono- and poly(ADP-ribose) signals that are important for the subsequent decompaction of chromatin and the recruitment of repair factors3,4. |
| GO:0140808 NAD+-protein-tyrosine ADP-ribosyltransferase activity | IDA PMID:29954836 Comprehensive ADP-ribosylome analysis identifies tyrosine as... | KEEP AS NON CORE | Summary: PARP1/HPF1 can modify tyrosine residues; tyrosine ADP-ribosylation sites were identified in proteomic datasets. Reason: Tyrosine ADP-ribosylation by PARP1/HPF1 is supported by proteomic site identification but is a minor acceptor compared with serine. Kept as non-core. Supporting Evidence: PMID:29954836 Here, we report the establishment of an unbiased, multistep ADP-ribosylome data analysis workflow that led to the identification of tyrosine as a novel ARTD1/PARP1-dependent in vivo ADPr-acceptor amino acid. PMID:30257210 Furthermore, by characterizing the PARP/HPF1-catalyzed ADPr consensus motif, we determine the relative significance of the preceding basic residue and discover tyrosine as an acceptor for ADPr. |
| GO:0140808 NAD+-protein-tyrosine ADP-ribosyltransferase activity | IDA PMID:30257210 Interplay of Histone Marks with Serine ADP-Ribosylation. | KEEP AS NON CORE | Summary: PARP1/HPF1 can modify tyrosine residues; tyrosine ADP-ribosylation sites were identified in proteomic datasets. Reason: Tyrosine ADP-ribosylation by PARP1/HPF1 is supported by proteomic site identification but is a minor acceptor compared with serine. Kept as non-core. Supporting Evidence: PMID:30257210 Furthermore, by characterizing the PARP/HPF1-catalyzed ADPr consensus motif, we determine the relative significance of the preceding basic residue and discover tyrosine as an acceptor for ADPr. PMID:29954836 Here, we report the establishment of an unbiased, multistep ADP-ribosylome data analysis workflow that led to the identification of tyrosine as a novel ARTD1/PARP1-dependent in vivo ADPr-acceptor amino acid. |
| GO:0140808 NAD+-protein-tyrosine ADP-ribosyltransferase activity | IEA GO_REF:0000116 | KEEP AS NON CORE | Summary: PARP1/HPF1 can modify tyrosine residues; tyrosine ADP-ribosylation sites were identified in proteomic datasets. Reason: Tyrosine ADP-ribosylation by PARP1/HPF1 is supported by proteomic site identification but is a minor acceptor compared with serine. Kept as non-core. Supporting Evidence: PMID:29954836 Here, we report the establishment of an unbiased, multistep ADP-ribosylome data analysis workflow that led to the identification of tyrosine as a novel ARTD1/PARP1-dependent in vivo ADPr-acceptor amino acid. PMID:30257210 Furthermore, by characterizing the PARP/HPF1-catalyzed ADPr consensus motif, we determine the relative significance of the preceding basic residue and discover tyrosine as an acceptor for ADPr. |
| GO:0140815 NAD+-protein-histidine ADP-ribosyltransferase activity | IDA PMID:35393539 Poly(ADP-ribosylation) of P-TEFb by PARP1 disrupts phase sep... | KEEP AS NON CORE | Summary: PARP1 was reported to ADP-ribosylate histidine residues of cyclin T1 after DNA damage, inactivating P-TEFb. Reason: Histidine modification is reported for a specific substrate (CycT1) in one study; real but a minor, context-specific acceptor. Kept as non-core. Supporting Evidence: PMID:35393539 Here we report that PARP1 inhibits Pol II elongation by inactivating the transcription elongation factor P-TEFb, a CDK9-cyclin T1 (CycT1) heterodimer. PMID:35393539 After sensing damage, the activated PARP1 binds to transcriptionally engaged P-TEFb and modifies CycT1 at multiple positions, including histidine residues that are rarely used as an acceptor site. |
| GO:0140815 NAD+-protein-histidine ADP-ribosyltransferase activity | IEA GO_REF:0000116 | KEEP AS NON CORE | Summary: PARP1 was reported to ADP-ribosylate histidine residues of cyclin T1 after DNA damage, inactivating P-TEFb. Reason: Histidine modification is reported for a specific substrate (CycT1) in one study; real but a minor, context-specific acceptor. Kept as non-core. Supporting Evidence: PMID:35393539 Here we report that PARP1 inhibits Pol II elongation by inactivating the transcription elongation factor P-TEFb, a CDK9-cyclin T1 (CycT1) heterodimer. |
| GO:0140816 NAD+-histone H2BS6 serine ADP-ribosyltransferase activity | IDA PMID:34874266 Serine ADP-ribosylation marks nucleosomes for ALC1-dependent... | ACCEPT | Summary: PARP1/HPF1 ADP-ribosylates histone H2B on Ser6, a DNA damage-induced mark that converts nucleosomes into ALC1 substrates. Reason: Directly demonstrated with semisynthetic, site-specifically ADP-ribosylated nucleosomes; histone serine marks are a principal output of PARP1/HPF1 in the DNA damage response. Supporting Evidence: PMID:34874266 Serine ADP-ribosylation (ADPr) is a DNA damage-induced post-translational modification catalyzed by the PARP1/2:HPF1 complex. PMID:34874266 This chemoenzymatic protein synthesis strategy was employed to assemble a series of full-length, ADP-ribosylated histones and show that ADPr at histone H2B serine 6 or histone H3 serine 10 converts nucleosomes into robust substrates for the chromatin remodeler ALC1. |
| GO:0140817 NAD+-histone H3S10 serine ADP-ribosyltransferase activity | IDA PMID:34874266 Serine ADP-ribosylation marks nucleosomes for ALC1-dependent... | ACCEPT | Summary: PARP1/HPF1 ADP-ribosylates histone H3 on Ser10 at sites of DNA damage. Reason: Directly demonstrated in the same chemoenzymatic nucleosome study; a principal histone serine mark of PARP1/HPF1. Supporting Evidence: PMID:34874266 Serine ADP-ribosylation (ADPr) is a DNA damage-induced post-translational modification catalyzed by the PARP1/2:HPF1 complex. PMID:34874266 This chemoenzymatic protein synthesis strategy was employed to assemble a series of full-length, ADP-ribosylated histones and show that ADPr at histone H2B serine 6 or histone H3 serine 10 converts nucleosomes into robust substrates for the chromatin remodeler ALC1. |
| GO:0140822 NAD+-histone H2BE35 glutamate ADP-ribosyltransferase activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Transferred by sequence similarity: PARP1 mono-ADP-ribosylates histone H2B Glu35, a mark reported in adipocyte differentiation. Reason: The H2B E35 mark is a specific, context-dependent activity transferred from the rodent ortholog by curator judgement; plausible given conserved active site, but not part of the DNA damage core. Kept as non-core. Supporting Evidence: PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. |
| GO:0160049 negative regulation of cGAS/STING signaling pathway | IDA PMID:35460603 Cytoplasmic PARP1 links the genome instability to the inhibi... | KEEP AS NON CORE | Summary: PARP1 PARylates cGAS on Asp191, inhibiting cGAS/STING signalling. Reason: Experimentally supported; non-core. Supporting Evidence: PMID:35460603 Activated DNA-PK phosphorylates PARP1 on Thr594, thus facilitating the cytoplasmic translocation of PARP1 to inhibit the antiviral immunity both in vitro and in vivo. PMID:35460603 Mechanistically, cytoplasmic PARP1 interacts with and directly PARylates cyclic GMP-AMP synthase (cGAS) on Asp191 to inhibit its DNA-binding ability. |
| GO:1900182 positive regulation of protein localization to nucleus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog projection: PARP1 promotes nuclear localization of some proteins. Reason: Non-core. |
| GO:1901701 cellular response to oxygen-containing compound | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Electronic annotation: cellular response to oxygen-containing compound. Reason: Broad term consistent with PARP1 activation by oxidative DNA damage; non-core. |
| GO:1903376 regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog projection: PARP1 regulates oxidative stress-induced neuronal intrinsic apoptotic signalling. Reason: Consistent with PARP1-dependent neuronal death (parthanatos) after oxidative stress; non-core. Supporting Evidence: PMID:12114629 We show that PARP-1 activation is required for translocation of apoptosis-inducing factor (AIF) from the mitochondria to the nucleus and that AIF is necessary for PARP-1-dependent cell death. |
| GO:1904044 response to aldosterone | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog projection: response to aldosterone. Reason: Rodent physiology; over-annotation. |
| GO:1904178 negative regulation of adipose tissue development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Transferred by sequence similarity: negative regulation of adipose tissue development (via H2B E35 mono-ADP-ribosylation). Reason: Reported mechanism in adipogenesis; non-core. |
| GO:1904357 negative regulation of telomere maintenance via telomere lengthening | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Transferred by sequence similarity: PARP1 negatively regulates telomere lengthening. Reason: Ortholog transfer of a reported telomere role; plausible, non-core. |
| GO:1904646 cellular response to amyloid-beta | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog projection: cellular response to amyloid-beta. Reason: Amyloid-beta-induced oxidative DNA damage activates PARP1 in neurons; non-core. |
| GO:1904762 positive regulation of myofibroblast differentiation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog projection: positive regulation of myofibroblast differentiation. Reason: Tissue-level physiology from rodent studies; over-annotation for a broadly acting DNA damage enzyme. |
| GO:1905051 regulation of base-excision repair | IDA PMID:34102106 XRCC1 prevents toxic PARP1 trapping during DNA base excision... | ACCEPT | Summary: PARP1 regulates base excision repair: it accelerates BER but must be released by XRCC1-dependent mechanisms; unreleased PARP1 impedes BER. Reason: Directly supported; reflects PARP1 core role at BER intermediates. Supporting Evidence: PMID:34102106 PARPs are sensors that detect single-strand break intermediates, but the critical role of XRCC1 during BER is unknown. PMID:34102106 Consequently, PARP1 deletion rescues BER and resistance to base damage in XRCC1-/- cells. |
| GO:1905168 positive regulation of double-strand break repair via homologous recombination | IDA PMID:26344098 Timeless Interacts with PARP-1 to Promote Homologous Recombi... | KEEP AS NON CORE | Summary: PARP1 promotes homologous recombination via Timeless recruitment; nuclear cGAS antagonises this. Reason: Experimentally supported regulatory role; non-core relative to the core DSB repair annotation. Supporting Evidence: PMID:26344098 We demonstrate that rapid and transient accumulation of Timeless at laser-induced DNA damage sites requires PARP-1, but not poly(ADP-ribosyl)ation and that Timeless is co-trapped with PARP-1 at DNA lesions upon PARP inhibition. PMID:30356214 In the nucleus, cGAS is recruited to double-stranded breaks and interacts with PARP1 via poly(ADP-ribose). |
| GO:1905168 positive regulation of double-strand break repair via homologous recombination | IDA PMID:30356214 Nuclear cGAS suppresses DNA repair and promotes tumorigenesi... | KEEP AS NON CORE | Summary: PARP1 promotes homologous recombination via Timeless recruitment; nuclear cGAS antagonises this. Reason: Experimentally supported regulatory role; non-core relative to the core DSB repair annotation. Supporting Evidence: PMID:30356214 In the nucleus, cGAS is recruited to double-stranded breaks and interacts with PARP1 via poly(ADP-ribose). PMID:30356214 The cGAS-PARP1 interaction impedes the formation of the PARP1-Timeless complex, and thereby suppresses homologous recombination. PMID:26344098 We demonstrate that rapid and transient accumulation of Timeless at laser-induced DNA damage sites requires PARP-1, but not poly(ADP-ribosyl)ation and that Timeless is co-trapped with PARP-1 at DNA lesions upon PARP inhibition. |
| GO:1990090 cellular response to nerve growth factor stimulus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog projection: cellular response to nerve growth factor stimulus. Reason: No evidence of a specific PARP1 role in NGF responses; over-annotation. |
| GO:1990165 single-strand break-containing DNA binding | IDA PMID:36323657 Structural dynamics of DNA strand break sensing by PARP-1 at... | ACCEPT | Summary: PARP1 binds single-strand break-containing DNA through its N-terminal zinc fingers, which kink the DNA at the break. Reason: Single-molecule FRET and structural ensemble data show direct SSB recognition; this is the most specific DNA-binding term for PARP1 core sensor function. Supporting Evidence: PMID:36323657 Quantitative smFRET and structural ensemble calculations reveal how PARP-1's N-terminal zinc fingers convert DNA SSBs from a largely unperturbed conformation, via an intermediate state into the highly kinked DNA conformation. PMID:36323657 Our data suggest an induced fit mechanism via a multi-domain assembly cascade that drives SSB sensing and stimulates an interplay with the scaffold protein XRCC1 orchestrating subsequent DNA repair events. PMID:26626479 Poly(ADP-ribose)polymerase 1 (PARP-1) is a key eukaryotic stress sensor that responds in seconds to DNA single-strand breaks (SSBs), the most frequent genomic damage. |
| GO:1990404 NAD+-protein mono-ADP-ribosyltransferase activity | IDA PMID:19764761 Identification of the ADP-ribosylation sites in the PARP-1 a... | ACCEPT | Summary: PARP1 performs mono-ADP-ribosylation as the initiating step of ADP-ribosylation; with HPF1, serine ADP-ribosylation in cells exists mainly as mono-ADP-ribose. Reason: Mono-ADP-ribosyl transfer is the initiation step of the PARP1 reaction and the predominant product of PARP1/HPF1 at serine sites in cells, demonstrated biochemically and by proteomics. This is a genuine activity of PARP1 (subsumed in the overall ADP-ribosyltransferase function) and is accepted. Supporting Evidence: PMID:19764761 Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins and itself using NAD(+) as a substrate. PMID:19764761 Here we report a strategy to identify the modification sites on domain D using the PARP-1 E988Q mutant, which only catalyzes mono(ADP-ribosyl)ation. PMID:34625544 Our data support the notion that serine ADP-ribosylation mainly exists as mono-ADP-ribosylation in cells, and reveal a remarkable degree of histone co-modification with serine ADP-ribosylation and other post-translational modifications. |
| GO:1990404 NAD+-protein mono-ADP-ribosyltransferase activity | IDA PMID:24906880 PARG is dispensable for recovery from transient replicative ... | ACCEPT | Summary: PARP1 performs mono-ADP-ribosylation as the initiating step of ADP-ribosylation; with HPF1, serine ADP-ribosylation in cells exists mainly as mono-ADP-ribose. Reason: Mono-ADP-ribosyl transfer is the initiation step of the PARP1 reaction and the predominant product of PARP1/HPF1 at serine sites in cells, demonstrated biochemically and by proteomics. This is a genuine activity of PARP1 (subsumed in the overall ADP-ribosyltransferase function) and is accepted. Supporting Evidence: PMID:24906880 The founding member of the PARP family PARP-1 is a key regulator of DNA damage repair, by controlling the recruitment or repellence of DNA repair enzymes as well as chromatin structure modifiers to accelerate repair (1,2). PMID:34625544 Our data support the notion that serine ADP-ribosylation mainly exists as mono-ADP-ribosylation in cells, and reveal a remarkable degree of histone co-modification with serine ADP-ribosylation and other post-translational modifications. PMID:25043379 Here we show that the majority of PARPs generate MAR, not PAR, and demonstrate that the H-Y-E motif is not the sole indicator of PARP activity. |
| GO:1990404 NAD+-protein mono-ADP-ribosyltransferase activity | IDA PMID:25043379 Family-wide analysis of poly(ADP-ribose) polymerase activity... | ACCEPT | Summary: PARP1 performs mono-ADP-ribosylation as the initiating step of ADP-ribosylation; with HPF1, serine ADP-ribosylation in cells exists mainly as mono-ADP-ribose. Reason: Mono-ADP-ribosyl transfer is the initiation step of the PARP1 reaction and the predominant product of PARP1/HPF1 at serine sites in cells, demonstrated biochemically and by proteomics. This is a genuine activity of PARP1 (subsumed in the overall ADP-ribosyltransferase function) and is accepted. Supporting Evidence: PMID:25043379 Here we show that the majority of PARPs generate MAR, not PAR, and demonstrate that the H-Y-E motif is not the sole indicator of PARP activity. PMID:25043379 We identify automodification sites on seven PARPs, and demonstrate that MAR and PAR generating PARPs modify similar amino acids, suggesting that the sequence and structural constraints limiting PARPs to MAR synthesis do not limit their ability to modify canonical amino-acid targets. PMID:34625544 Our data support the notion that serine ADP-ribosylation mainly exists as mono-ADP-ribosylation in cells, and reveal a remarkable degree of histone co-modification with serine ADP-ribosylation and other post-translational modifications. |
| GO:1990404 NAD+-protein mono-ADP-ribosyltransferase activity | IDA PMID:25533949 A human tRNA synthetase is a potent PARP1-activating effecto... | ACCEPT | Summary: PARP1 performs mono-ADP-ribosylation as the initiating step of ADP-ribosylation; with HPF1, serine ADP-ribosylation in cells exists mainly as mono-ADP-ribose. Reason: Mono-ADP-ribosyl transfer is the initiation step of the PARP1 reaction and the predominant product of PARP1/HPF1 at serine sites in cells, demonstrated biochemically and by proteomics. This is a genuine activity of PARP1 (subsumed in the overall ADP-ribosyltransferase function) and is accepted. Supporting Evidence: PMID:25533949 Resveratrol nullifies the catalytic activity and redirects TyrRS to a nuclear function, stimulating NAD(+)-dependent auto-poly-ADP-ribosylation of poly(ADP-ribose) polymerase 1 (PARP1). PMID:34625544 Our data support the notion that serine ADP-ribosylation mainly exists as mono-ADP-ribosylation in cells, and reveal a remarkable degree of histone co-modification with serine ADP-ribosylation and other post-translational modifications. PMID:25043379 Here we show that the majority of PARPs generate MAR, not PAR, and demonstrate that the H-Y-E motif is not the sole indicator of PARP activity. |
| GO:1990404 NAD+-protein mono-ADP-ribosyltransferase activity | IDA PMID:26344098 Timeless Interacts with PARP-1 to Promote Homologous Recombi... | ACCEPT | Summary: PARP1 performs mono-ADP-ribosylation as the initiating step of ADP-ribosylation; with HPF1, serine ADP-ribosylation in cells exists mainly as mono-ADP-ribose. Reason: Mono-ADP-ribosyl transfer is the initiation step of the PARP1 reaction and the predominant product of PARP1/HPF1 at serine sites in cells, demonstrated biochemically and by proteomics. This is a genuine activity of PARP1 (subsumed in the overall ADP-ribosyltransferase function) and is accepted. Supporting Evidence: PMID:26344098 We demonstrate that rapid and transient accumulation of Timeless at laser-induced DNA damage sites requires PARP-1, but not poly(ADP-ribosyl)ation and that Timeless is co-trapped with PARP-1 at DNA lesions upon PARP inhibition. PMID:34625544 Our data support the notion that serine ADP-ribosylation mainly exists as mono-ADP-ribosylation in cells, and reveal a remarkable degree of histone co-modification with serine ADP-ribosylation and other post-translational modifications. PMID:25043379 Here we show that the majority of PARPs generate MAR, not PAR, and demonstrate that the H-Y-E motif is not the sole indicator of PARP activity. |
| GO:1990404 NAD+-protein mono-ADP-ribosyltransferase activity | IDA PMID:28190768 Serine ADP-Ribosylation Depends on HPF1. | ACCEPT | Summary: PARP1 performs mono-ADP-ribosylation as the initiating step of ADP-ribosylation; with HPF1, serine ADP-ribosylation in cells exists mainly as mono-ADP-ribose. Reason: Mono-ADP-ribosyl transfer is the initiation step of the PARP1 reaction and the predominant product of PARP1/HPF1 at serine sites in cells, demonstrated biochemically and by proteomics. This is a genuine activity of PARP1 (subsumed in the overall ADP-ribosyltransferase function) and is accepted. Supporting Evidence: PMID:28190768 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. PMID:28190768 Moreover, adding HPF1 to in vitro PARP-1/PARP-2 reactions is necessary and sufficient for serine-specific ADPr of histones and PARP-1 itself. PMID:34625544 Our data support the notion that serine ADP-ribosylation mainly exists as mono-ADP-ribosylation in cells, and reveal a remarkable degree of histone co-modification with serine ADP-ribosylation and other post-translational modifications. |
| GO:1990404 NAD+-protein mono-ADP-ribosyltransferase activity | IDA PMID:31796734 Barrier-to-autointegration factor 1 (Banf1) regulates poly [... | ACCEPT | Summary: PARP1 performs mono-ADP-ribosylation as the initiating step of ADP-ribosylation; with HPF1, serine ADP-ribosylation in cells exists mainly as mono-ADP-ribose. Reason: Mono-ADP-ribosyl transfer is the initiation step of the PARP1 reaction and the predominant product of PARP1/HPF1 at serine sites in cells, demonstrated biochemically and by proteomics. This is a genuine activity of PARP1 (subsumed in the overall ADP-ribosyltransferase function) and is accepted. Supporting Evidence: PMID:31796734 Specifically, oxidative lesions promote direct binding of Banf1 to PARP1, a critical NAD+-dependent DNA repair protein, leading to inhibition of PARP1 auto-ADP-ribosylation and defective repair of oxidative lesions, in cells with increased Banf1. PMID:34625544 Our data support the notion that serine ADP-ribosylation mainly exists as mono-ADP-ribosylation in cells, and reveal a remarkable degree of histone co-modification with serine ADP-ribosylation and other post-translational modifications. PMID:25043379 Here we show that the majority of PARPs generate MAR, not PAR, and demonstrate that the H-Y-E motif is not the sole indicator of PARP activity. |
| GO:1990404 NAD+-protein mono-ADP-ribosyltransferase activity | IDA PMID:32028527 HPF1 completes the PARP active site for DNA damage-induced A... | ACCEPT | Summary: PARP1 performs mono-ADP-ribosylation as the initiating step of ADP-ribosylation; with HPF1, serine ADP-ribosylation in cells exists mainly as mono-ADP-ribose. Reason: Mono-ADP-ribosyl transfer is the initiation step of the PARP1 reaction and the predominant product of PARP1/HPF1 at serine sites in cells, demonstrated biochemically and by proteomics. This is a genuine activity of PARP1 (subsumed in the overall ADP-ribosyltransferase function) and is accepted. Supporting Evidence: PMID:32028527 After binding to genomic lesions, these enzymes use NAD+ to modify numerous proteins with mono- and poly(ADP-ribose) signals that are important for the subsequent decompaction of chromatin and the recruitment of repair factors3,4. PMID:32028527 These post-translational modifications are predominantly serine-linked and require the accessory factor HPF1, which is specific for the DNA damage response and switches the amino acid specificity of PARP1 and PARP2 from aspartate or glutamate to serine residues5-10. PMID:34625544 Our data support the notion that serine ADP-ribosylation mainly exists as mono-ADP-ribosylation in cells, and reveal a remarkable degree of histone co-modification with serine ADP-ribosylation and other post-translational modifications. |
| GO:1990404 NAD+-protein mono-ADP-ribosyltransferase activity | IDA PMID:33186521 An HPF1/PARP1-Based Chemical Biology Strategy for Exploring ... | ACCEPT | Summary: PARP1 performs mono-ADP-ribosylation as the initiating step of ADP-ribosylation; with HPF1, serine ADP-ribosylation in cells exists mainly as mono-ADP-ribose. Reason: Mono-ADP-ribosyl transfer is the initiation step of the PARP1 reaction and the predominant product of PARP1/HPF1 at serine sites in cells, demonstrated biochemically and by proteomics. This is a genuine activity of PARP1 (subsumed in the overall ADP-ribosyltransferase function) and is accepted. Supporting Evidence: PMID:33186521 An HPF1/PARP1-Based Chemical Biology Strategy for Exploring ADP-Ribosylation. PMID:34625544 Our data support the notion that serine ADP-ribosylation mainly exists as mono-ADP-ribosylation in cells, and reveal a remarkable degree of histone co-modification with serine ADP-ribosylation and other post-translational modifications. PMID:25043379 Here we show that the majority of PARPs generate MAR, not PAR, and demonstrate that the H-Y-E motif is not the sole indicator of PARP activity. |
| GO:1990404 NAD+-protein mono-ADP-ribosyltransferase activity | IDA PMID:34049076 PARP1-mediated PARylation of TonEBP prevents R-loop-associat... | ACCEPT | Summary: PARP1 performs mono-ADP-ribosylation as the initiating step of ADP-ribosylation; with HPF1, serine ADP-ribosylation in cells exists mainly as mono-ADP-ribose. Reason: Mono-ADP-ribosyl transfer is the initiation step of the PARP1 reaction and the predominant product of PARP1/HPF1 at serine sites in cells, demonstrated biochemically and by proteomics. This is a genuine activity of PARP1 (subsumed in the overall ADP-ribosyltransferase function) and is accepted. Supporting Evidence: PMID:34049076 PARP1-mediated PARylation was required for recruitment of TonEBP to the sites of R-loop-associated DNA damage. PMID:34625544 Our data support the notion that serine ADP-ribosylation mainly exists as mono-ADP-ribosylation in cells, and reveal a remarkable degree of histone co-modification with serine ADP-ribosylation and other post-translational modifications. PMID:25043379 Here we show that the majority of PARPs generate MAR, not PAR, and demonstrate that the H-Y-E motif is not the sole indicator of PARP activity. |
| GO:1990404 NAD+-protein mono-ADP-ribosyltransferase activity | IDA PMID:34102106 XRCC1 prevents toxic PARP1 trapping during DNA base excision... | ACCEPT | Summary: PARP1 performs mono-ADP-ribosylation as the initiating step of ADP-ribosylation; with HPF1, serine ADP-ribosylation in cells exists mainly as mono-ADP-ribose. Reason: Mono-ADP-ribosyl transfer is the initiation step of the PARP1 reaction and the predominant product of PARP1/HPF1 at serine sites in cells, demonstrated biochemically and by proteomics. This is a genuine activity of PARP1 (subsumed in the overall ADP-ribosyltransferase function) and is accepted. Supporting Evidence: PMID:34102106 PARPs are sensors that detect single-strand break intermediates, but the critical role of XRCC1 during BER is unknown. PMID:34102106 Consequently, PARP1 deletion rescues BER and resistance to base damage in XRCC1-/- cells. PMID:34625544 Our data support the notion that serine ADP-ribosylation mainly exists as mono-ADP-ribosylation in cells, and reveal a remarkable degree of histone co-modification with serine ADP-ribosylation and other post-translational modifications. |
| GO:1990404 NAD+-protein mono-ADP-ribosyltransferase activity | IDA PMID:34625544 The regulatory landscape of the human HPF1- and ARH3-depende... | ACCEPT | Summary: PARP1 performs mono-ADP-ribosylation as the initiating step of ADP-ribosylation; with HPF1, serine ADP-ribosylation in cells exists mainly as mono-ADP-ribose. Reason: Mono-ADP-ribosyl transfer is the initiation step of the PARP1 reaction and the predominant product of PARP1/HPF1 at serine sites in cells, demonstrated biochemically and by proteomics. This is a genuine activity of PARP1 (subsumed in the overall ADP-ribosyltransferase function) and is accepted. Supporting Evidence: PMID:34625544 Our data support the notion that serine ADP-ribosylation mainly exists as mono-ADP-ribosylation in cells, and reveal a remarkable degree of histone co-modification with serine ADP-ribosylation and other post-translational modifications. PMID:25043379 Here we show that the majority of PARPs generate MAR, not PAR, and demonstrate that the H-Y-E motif is not the sole indicator of PARP activity. |
| GO:1990404 NAD+-protein mono-ADP-ribosyltransferase activity | IDA PMID:7852410 Role of glutamic acid 988 of human poly-ADP-ribose polymeras... | ACCEPT | Summary: PARP1 performs mono-ADP-ribosylation as the initiating step of ADP-ribosylation; with HPF1, serine ADP-ribosylation in cells exists mainly as mono-ADP-ribose. Reason: Mono-ADP-ribosyl transfer is the initiation step of the PARP1 reaction and the predominant product of PARP1/HPF1 at serine sites in cells, demonstrated biochemically and by proteomics. This is a genuine activity of PARP1 (subsumed in the overall ADP-ribosyltransferase function) and is accepted. Supporting Evidence: PMID:7852410 Glu988 of the human polymerase aligns with the catalytic glutamic acid of the toxins, and replacement of this residue with Gln, Asp, or Ala caused major reductions in synthesis of enzyme-linked poly-ADP-ribose. PMID:34625544 Our data support the notion that serine ADP-ribosylation mainly exists as mono-ADP-ribosylation in cells, and reveal a remarkable degree of histone co-modification with serine ADP-ribosylation and other post-translational modifications. PMID:25043379 Here we show that the majority of PARPs generate MAR, not PAR, and demonstrate that the H-Y-E motif is not the sole indicator of PARP activity. |
| GO:1990966 ATP generation from poly-ADP-D-ribose | IDA PMID:27257257 ADP-ribose-derived nuclear ATP synthesis by NUDIX5 is requir... | MARK AS OVER ANNOTATED | Summary: Nuclear ATP synthesis from PAR-derived ADP-ribose by NUDT5 depends on PAR synthesis. Reason: NUDT5 catalyses ATP generation from ADP-ribose (after PARG hydrolysis of PAR); PARP1 supplies the polymer substrate but does not perform the ATP-generating step. Supporting Evidence: PMID:27257257 We analyzed this question in the context of the massive gene regulation changes induced by progestins in breast cancer cells and found that ATP is generated in the cell nucleus via the hydrolysis of poly(ADP-ribose) to ADP-ribose. |
| GO:2001170 negative regulation of ATP biosynthetic process | IMP PMID:24289924 Phosphorylation of p53 by TAF1 inactivates p53-dependent tra... | MARK AS OVER ANNOTATED | Summary: PARP1 activation depletes cellular ATP after DNA damage. Reason: ATP depletion is an indirect metabolic consequence of NAD+ consumption by hyperactive PARP1, not a regulatory function of PARP1. Supporting Evidence: PMID:24289924 Upon DNA damage, cells undergo PARP-1-dependent ATP depletion, which is correlated with reduced TAF1 kinase activity and Thr55 phosphorylation, resulting in p21 activation. |
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Download this section (compressed HTML)Q: Parthanatos is listed in GO only as a synonym of necroptotic process, although it needs neither RIPK3 nor MLKL. Should that synonym be removed or made a related synonym, and should PARP1/AIFM1 parthanatos annotations use programmed necrotic cell death instead?
Suggested experts: GO cell death curators, parthanatos researchers
Q: What fraction of PARP1 catalytic output in human cells is HPF1-dependent serine mono-ADP-ribosylation versus Asp/Glu-linked poly-ADP-ribosylation, and should both be considered core?
Suggested experts: ADP-ribosylation biochemists
Q: Is the reported intra-mitochondrial PARP1 pool physiologically relevant, given conflicting reports on mitochondrial PARylation and mtDNA repair?
Suggested experts: mitochondrial DNA repair experts
Q: Should DNA end ADP-ribosylation (GO:0140294) by PARP1 be considered physiological in human cells?
Suggested experts: DNA repair biochemists
Experiment: Quantify serine versus Asp/Glu ADP-ribosylation and chain length on endogenous PARP1 substrates in HPF1-knockout and catalytic-mutant (E988Q) knock-in human cells after defined DNA lesions.
Hypothesis: HPF1-dependent serine mono-ADP-ribosylation is the dominant PARP1 output for DNA repair signalling, while Asp/Glu PAR mainly mediates PARP1 release and parthanatos signalling.
Type: quantitative ADP-ribosylome mass spectrometry
Experiment: Use mitochondria-targeted versus nuclear-restricted PARP1 rescue constructs in PARP1-null cells and measure mtDNA repair, mitochondrial PARylation and parthanatos sensitivity.
Hypothesis: Nuclear PAR synthesis, not an intra-mitochondrial PARP1 pool, accounts for PARP1 effects on mitochondria and AIF release.
Type: compartment-restricted rescue
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