ERCC4 (XPF) is the catalytic subunit of the nuclear ERCC4–ERCC1 structure-specific DNA endonuclease. Its metal-dependent nuclease domain is distinct from the N-terminal helicase-like regulatory module, and C-terminal helix–hairpin–helix domains help assemble the heterodimer and engage DNA. The complex cleaves DNA junctions during nucleotide-excision repair and interstrand-crosslink repair and contributes to processing recombination intermediates. XPA and SLX4 organize recruitment in different repair contexts. A smaller fraction also participates in telomere-associated processes. Disease-associated ERCC4 variants can disrupt architecture, catalytic activity or recruitment to particular repair pathways; xeroderma pigmentosum and Fanconi anemia phenotypes therefore need not reflect the same intrinsic nuclease defect.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006312 mitotic recombination | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Conserved participation in mitotic recombination, retained as a contextual repair role. Reason: The actual IBD, family tree and target alignment support this inherited assertion. ERCC4 participates in processing recombination intermediates rather than merely responding to recombination damage; the independently traced Reactome single-strand-annealing events include ERCC1:ERCC4 in flap processing. The subsequently recovered PMID:14734547 original directly measures human RAD52–ERCC1/XPF interaction and junction incision (Methods/Results and Figures 1–4); it does not reconstitute complete chromosomal mitotic recombination. Retain the specialized mitotic context as non-core without treating donor count or the human target in WITH/FROM as a propagation defect. The current IBD additionally lists a mouse descendant; the imported source list is preserved. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000015911 SUPPORTS TRANSFER Official PAINT IBD at PTN000015911 in PTHR10150; the human Q92889 leaf PTN002468357 descends from this node, its ungapped MSA sequence matches the 916-aa canonical protein, and no NOT occurs on the inspected target path. No target-specific loss or incompatible clade placement was established; inclusion of Q92889 among experimental descendants is legitimate, not circular evidence. Supporting Evidence: PMID:22547097 ERCC1-XPF is a heterodimeric, structure-specific endonuclease that cleaves single-stranded/double-stranded DNA junctions and has roles in nucleotide excision repair (NER), interstrand crosslink (ICL) repair, homologous recombination, and possibly other pathways. |
| GO:1990599 3' overhang single-stranded DNA endonuclease activity | IBA GO_REF:0000033 | ACCEPT | Summary: Conserved contribution to 3′-overhang DNA endonuclease activity in the ERCC1–ERCC4 complex. Reason: The contributes_to assertion is supported by the verified PAINT node and target experimental grounding in PMID:14690602. Its accessible abstract reports retention of telomeric overhangs in ERCC1/XPF-deficient cells after TRF2 inhibition; it is not a purified overhang-incision assay. Independent human XPF–ERCC1 structure and stem-loop incision experiments in PMID:32111838 establish the catalytic complex and junction-dependent incision, without by themselves specifying every overhang cleavage position. Accept the curator’s specific complex-contribution assertion with these assay boundaries, rather than reinterpreting it as isolated ERCC4 exonuclease activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000015911 SUPPORTS TRANSFER Official PAINT IBD at PTN000015911 in PTHR10150; the human Q92889 leaf PTN002468357 descends from this node, its ungapped MSA sequence matches the 916-aa canonical protein, and no NOT occurs on the inspected target path. No target-specific loss or incompatible clade placement was established; inclusion of Q92889 among experimental descendants is legitimate, not circular evidence. Supporting Evidence: PMID:14690602 ERCC1/XPF-deficient cells retained the telomeric overhang after TRF2 inhibition, identifying this nucleotide excision repair endonuclease as the culprit in overhang removal. |
| GO:1901255 nucleotide-excision repair involved in interstrand cross-link repair | IBA GO_REF:0000033 | ACCEPT | Summary: The ERCC1–ERCC4 nuclease contributes incision activity to interstrand-crosslink repair. Reason: The PAINT placement is verified and agrees with human evidence. PMID:11790111 Methods and Results use normal human chromatin extracts and a site-specific psoralen crosslink: mapped anti-XPF antibodies inhibit the incisions. PMID:32034146 Results and Figure 7c show XPF-knockout HeLa cells are MMC-sensitive and wild-type XPF rescues this defect. The incision evidence supplies a functional step, while the survival experiment independently supports pathway participation; it does not alone locate every unhooking cut. Retain this established repair role without claiming that every ICL pathway uses an identical incision sequence. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000015911 SUPPORTS TRANSFER Official PAINT IBD at PTN000015911 in PTHR10150; the human Q92889 leaf PTN002468357 descends from this node, its ungapped MSA sequence matches the 916-aa canonical protein, and no NOT occurs on the inspected target path. No target-specific loss or incompatible clade placement was established; inclusion of Q92889 among experimental descendants is legitimate, not circular evidence. Supporting Evidence: PMID:32034146 The XPF-ERCC1 heterodimer is a structure-specific endonuclease that is essential for nucleotide excision repair (NER) and interstrand crosslink (ICL) repair in mammalian cells. PMID:23623386 the identified FA-causing ERCC4 mutations strongly disrupt the function of XPF in DNA ICL repair without severely compromising nucleotide excision repair. |
| GO:0000110 nucleotide-excision repair factor 1 complex | IBA GO_REF:0000033 | ACCEPT | Summary: ERCC4 is a component of the XPA-containing nucleotide-excision repair factor 1 complex. Reason: Current GO:0000110 explicitly includes human ERCC4/XPF, ERCC1 and XPA; it is not simply a synonym for the ERCC1–ERCC4 heterodimer. The verified PAINT node supports membership, and target-specific Reactome pre-incision participants place ERCC4 in the XPA-containing NER assembly. PMID:32111838 independently establishes the human heterodimer and discusses its XPA-binding region; its placement into a larger TFIIH–XPA assembly is a structural model, not a measured complete NEF1 structure. Accept membership with the corrected complex definition. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000015911 SUPPORTS TRANSFER Official PAINT IBD at PTN000015911 in PTHR10150; the human Q92889 leaf PTN002468357 descends from this node, its ungapped MSA sequence matches the 916-aa canonical protein, and no NOT occurs on the inspected target path. No target-specific loss or incompatible clade placement was established; inclusion of Q92889 among experimental descendants is legitimate, not circular evidence. |
| GO:0000712 resolution of meiotic recombination intermediates | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetically supported meiotic recombination-intermediate processing, retained as non-core. Reason: The target actually descends from the asserted PAINT node. Operative donor evidence is positive: C. elegans xpf-1 mutant combinations in PMID:23901331 Results/Figures 3–5 produce unresolved meiotic chromosome linkages that depend on SPO-11 and are restored by induced breaks; Drosophila mei-9 experiments in PMID:17339219 Methods and Results show strongly reduced crossovers and distinguish the phenotype from mismatch repair. These are genetic resolution assays, not purified human Holliday-junction cleavage. They support the conserved process assignment while its specific meiotic context remains non-core for this human repair enzyme. The PMID:23901331 correction changes funding only. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000015911 SUPPORTS TRANSFER Official PAINT IBD at PTN000015911 in PTHR10150; the human Q92889 leaf PTN002468357 descends from this node, its ungapped MSA sequence matches the 916-aa canonical protein, and no NOT occurs on the inspected target path. No target-specific loss or incompatible clade placement was established; inclusion of Q92889 among experimental descendants is legitimate, not circular evidence. Supporting Evidence: PMID:10644440 support a distinct role for the XPF/ERCC1 junction-specific endonuclease during meiosis, most likely in the resolution of heteroduplex intermediates that arise during recombination. |
| GO:0000724 double-strand break repair via homologous recombination | IBA GO_REF:0000033 | UNDECIDED | Summary: The PAINT inheritance path is verified, but the exact template-based homologous-recombination process remains unresolved in this source-specific assessment. Reason: The official PAINT IBD for GO:0000724 is placed at PTN000015911 in PTHR10150. Human Q92889 descends from that node, its ungapped MSA matches the 916-aa canonical sequence, and no NOT occurs on the inspected target path. The experimental descendants are legitimate: current QuickGO records trace human Q92889 to PMID:14728600, fission-yeast P36617 to PMID:12628934, Dictyostelium Q54PN5 to PMID:19763158, and Arabidopsis Q9LKI5/AT5G41150 to PMID:12393748, all with IMP evidence. Their operative template-based homologous-recombination assays were not verified in this review; the human PMID:14728600 remains abstract-only. The independently read human PMID:14734547 and Reactome R-HSA-5686657 support junction incision in single-strand annealing, but current GO:0045002 and its nonhomologous-end-removal step GO:0000736 are not descendants of GO:0000724. The previous rationale incorrectly treated SSA as such a descendant. Therefore retain explicit uncertainty for this exact process, without alleging incorrect PAINT placement, target-specific loss, circularity, weak donor count, or biological absence. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000015911 UNRESOLVED The IBD node, target descent, canonical MSA match, experimental descendant identities and absence of a target-path NOT are verified. The unresolved component is the exact biological process under the current GO:0000724 definition: operative assays underlying the descendant IMP assertions were not read, and independent SSA cleavage evidence does not supply that ontology bridge. This is not a finding of incorrect node placement or loss. Supporting Evidence: PMID:14734547 The XPF/ERCC1 heterodimer is a DNA structure-specific endonuclease that participates in nucleotide excision repair and homology-dependent recombination reactions, including DNA single strand annealing and gene targeting. |
| GO:0003684 damaged DNA binding | IBA GO_REF:0000033 | UNDECIDED | Summary: The phylogenetic placement is valid, but the exact damaged-DNA-binding activity remains unresolved. Reason: Current GO:0003684 requires binding to damaged DNA. The target donor annotation traces to PMID:11790111: the recovered Methods/Results measure anti-XPF-antibody effects on incision of crosslinked DNA by human chromatin extracts, and the Discussion infers a DNA-binding contribution from this and earlier work. This is positive repair evidence, but the inspected experiments do not isolate ERCC4 binding to the damaged substrate from recruitment, complex assembly and incision. Human ssDNA/junction binding in PMID:22483113 and PMID:32111838 does not independently settle this damage-specific substrate claim. Retain uncertainty about the molecular-function scope, not a claim of wrong ancestry, circular self-WITH, or absence of DNA binding. The inherited quotation is retained as repair context rather than treated as a binding assay. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000015911 UNRESOLVED Official PAINT IBD at PTN000015911 in PTHR10150; the human Q92889 leaf PTN002468357 descends from this node, its ungapped MSA sequence matches the 916-aa canonical protein, and no NOT occurs on the inspected target path. Ancestry is established; the exact damaged-DNA-binding interpretation of the target donor experiment remains unresolved. Supporting Evidence: PMID:11790111 XPF forms a heterodimeric complex with ERCC1 and is required for the repair of DNA interstrand cross-links. |
| GO:0003697 single-stranded DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: ERCC4 has directly supported single-stranded DNA-binding capacity. Reason: The PAINT path is verified. Independent official structural deposition 2KN7 identifies human Q92889 residues 842–908 in an NMR complex with 10-nucleotide ssDNA; this supports the binding claim even though the complete PMID:22483113 article was inaccessible. The construct is an isolated 67-aa C-terminal fragment, not the 372-aa natural product or evidence for physiological full-length homodimers. PMID:32111838 provides complementary human heterodimer/junction-recognition evidence, with its ssDNA-contact geometry partly modeled. Accept ssDNA binding while preserving construct and access limits. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000015911 SUPPORTS TRANSFER Official PAINT IBD at PTN000015911 in PTHR10150; the human Q92889 leaf PTN002468357 descends from this node, its ungapped MSA sequence matches the 916-aa canonical protein, and no NOT occurs on the inspected target path. No target-specific loss or incompatible clade placement was established; inclusion of Q92889 among experimental descendants is legitimate, not circular evidence. Supporting Evidence: PMID:22483113 A positively charged region within the second helix of the first HhH motif contacts the ssDNA phosphate backbone. |
| GO:0003677 DNA binding | IEA GO_REF:0000002 | ACCEPT | Summary: The actual IPR006166 match supports broad DNA-binding capacity. Reason: InterPro maps GO:0003677 through IPR006166, a domain spanning residues 683–814 in the official human target record. This is compatible with independently established human XPF DNA recognition: 2KN7/PMID:22483113 shows direct ssDNA binding by the C-terminal fragment, and PMID:32111838 measures binding of the human heterodimer to a stem-loop junction. Those independent data establish the broad annotation; they do not show that every contact or every natural product is represented by the IPR006166 interval. Retain the broad electronic assertion without substituting the unresolved damaged-DNA-binding claim. |
| GO:0003697 single-stranded DNA binding | IEA GO_REF:0000002 | ACCEPT | Summary: The XPF-family mapping is consistent with directly established ssDNA binding. Reason: The actual source IPR006167 is an XPF family entry matching residues 97–907, not a discrete ssDNA-binding domain. Its current GO mapping emits GO:0003697. Independent human fragment structure 2KN7 (PMID:22483113; Q92889 residues 842–908 and 10-nt ssDNA) supports the biological assertion. Full article access was unavailable, but the official experimental deposition identifies the construct and bound DNA. No equivalent activity is inferred for the short natural product. |
| GO:0004520 DNA endonuclease activity | IEA GO_REF:0000002 | MODIFY | Summary: Human ERCC4 supplies junction-specific duplex-DNA endonuclease activity within ERCC1–XPF. Reason: The verified IPR006167 mapping correctly identifies a DNA endonuclease, but GO:0106332 describes the established substrate geometry more precisely. Human full-length XPF–ERCC1 in PMID:32111838 cleaves a stem-loop substrate in a Mn-containing reaction. PMID:16076955 main Methods and Results, A Minimal, Structure-Specific Nuclease Derived from XPF–ERCC1, compare full-length human Sf9 enzyme and engineered truncations on junction substrates; neither preparation cleaves free ssDNA under the reported conditions. This refinement is based on independent human enzyme evidence, not on assuming that every family match or natural product is equivalent. Proposed replacements: ds/ssDNA junction-specific dsDNA endonuclease activity |
| GO:0005634 nucleus | IEA GO_REF:0000044 | MODIFY | Summary: Refine the broad nuclear location to independently observed nucleoplasm. Reason: The imported UniProt SL-0191 mapping correctly records nucleus. The actual human HPA ERCC4 record (ENSG00000175595) is more specific: both approved antibodies CAB000156 and HPA045828 report nucleoplasm in A-431, U-251MG and U2OS cells. Refine to GO:0005654 on this independent target evidence. These ICC/IF records do not resolve the two natural products separately and image pixels were not independently reassessed. Proposed replacements: nucleoplasm |
| GO:0005694 chromosome | IEA GO_REF:0000044 | ACCEPT | Summary: Chromosome-associated localization is consistent with ERCC4 recruitment to chromatin repair substrates. Reason: The actual UniProt location vocabulary maps SL-0468 to GO:0005694. Human chromatin-associated extracts in PMID:11790111 contain functional XPF, and the target-specific NER Reactome participant chains place the full-length human protein in DNA-bound repair assemblies. This supports chromosome association as a location, without treating all nucleoplasmic protein as constitutively chromosome-bound or inferring damage-selective binding as a separate molecular function. |
| GO:0006281 DNA repair | IEA GO_REF:0000120 | MODIFY | Summary: ERCC4 executes junction-incision steps in nucleotide-excision repair, interstrand-crosslink repair and SSA end processing. Reason: The actual ARBA00029008 predicates match IPR011335 plus Eukaryota and independently FunFam 3.40.50.10130:FF:000002; IPR006167 also emits DNA repair. Those mappings correctly identify repair but do not distinguish the executed routes. Human photolesion clearance and XPF rescue in PMID:32034146 support NER; human crosslinked-DNA incision in PMID:11790111 and the ERCC4 perturbations in PMID:19596235 support ICL repair. For SSA, human Reactome R-HSA-5686657 explicitly identifies ERCC1–ERCC4 as the catalytic active unit of flap removal, and PMID:14734547 Methods/Results and Figure 3 directly establish human RAD52-modulated junction incision. Refine broad DNA repair to these three nonredundant operations; the papers do not each assay all three. GO:0000736 describes the cleavage step, not annealing or template-based homologous recombination. Yeast Rad1/Rad10 same-role annotations corroborate the role convention; the existing human GO-CAM covers a separate NER context and is not evidence for the short product's activity. |
| GO:0009411 response to UV | IEA GO_REF:0000117 | ACCEPT | Summary: ERCC4 contributes to the cellular response to UV through nucleotide-excision repair. Reason: ARBA00028103 has an actual matching condition set requiring the two target FunFams 1.10.150.20:FF:000040 and 3.40.50.10130:FF:000002 plus Chordata, and emits GO:0009411. Independent human PMID:32034146 Results and Figure 7a–g demonstrate XPF-dependent clearance of UV photolesions and rescue with wild-type XPF. This is a direct repair contribution to UV response, not evidence that ERCC4 senses UV photons. A FunFam classification name mentioning an isoform does not establish activity of the short natural product. |
| GO:0005515 protein binding | IPI PMID:16338413 The structure of the human ERCC1/XPF interaction domains rev... | KEEP AS NON CORE | Summary: ERCC4 binds ERCC1 through its C-terminal heterodimerization module. Reason: The actual PMID:16338413 abstract describes human ERCC1–XPF C-terminal NMR heterodimer structures. This supports the named partnership, independently established by the inspected PMID:16076955 complex structure and biochemical work. The complete 16338413 original was unavailable, so no unseen residue-level or full-length construct claim is made. Retain the supported generic interaction as non-core. |
| GO:0005515 protein binding | IPI PMID:17289582 Identification of FAAP24, a Fanconi anemia core complex prot... | KEEP AS NON CORE | Summary: ERCC4 binds ERCC1, although this source's exact interaction assay was unavailable. Reason: The accessible PMID:17289582 abstract foregrounds FAAP24/FANCM; this does not establish that ERCC4 was absent from the full experiments. The exact ERCC4–ERCC1 partnership is independently established by inspected human heterodimer structures and biochemical experiments in PMID:16076955 and PMID:10413517. Retain the supported generic interaction as non-core, without claiming to have verified the uninspected IPI assay or alleging a wrong-gene annotation. |
| GO:0005515 protein binding | IPI PMID:19596235 Mammalian BTBD12/SLX4 assembles a Holliday junction resolvas... | KEEP AS NON CORE | Summary: ERCC4 associates with the human SLX4 nuclease scaffold. Reason: Inspected PMID:19596235 operative sections include human-cell affinity purification and U2OS endogenous immunoprecipitation, with peptide-competition and knockdown controls. These support the SLX4 association; the paper's SLX1/MUS81 junction-resolution chemistry must not be assigned to XPF. Retain generic binding as non-core rather than treating a positive interaction as over-annotation. Supporting Evidence: PMID:19596235 Human SLX4 forms a multiprotein complex with the ERCC4(XPF)-ERCC1, MUS81-EME1, and SLX1 endonucleases |
| GO:0005515 protein binding | IPI PMID:19596236 Human SLX4 is a Holliday junction resolvase subunit that bin... | KEEP AS NON CORE | Summary: Human XPF interacts with the N-terminal region of SLX4. Reason: PMID:19596236 Results and Methods describe human-cell co-immunoprecipitation and yeast two-hybrid assays that distinguish XPF contact from ERCC1. SLX4 constructs containing residues 1–1043 interact, whereas the tested 684–1834 fragment does not. These are engineered assay boundaries, not natural product assignments. Retain the supported generic interaction as non-core. |
| GO:0005515 protein binding | IPI PMID:24780295 Importance of EGFR/ERCC1 interaction following radiation-ind... | KEEP AS NON CORE | Summary: ERCC4 associates with ERCC1; the precise assay in this original remains uninspected. Reason: The available PMID:24780295 abstract describes EGFR–ERCC1 repair regulation; its full experimental coverage could not be inspected. This does not show that the ERCC4 IPI annotation is misattributed. Independently inspected human complex structures and biochemical experiments in PMID:16076955 and PMID:10413517 establish this exact partner relationship. Retain the supported generic interaction as non-core while preserving the original source and its assay-level access limitation. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: BioPlex 2.0 supports ERCC4–ERCC1 co-complex association. Reason: The actual BioPlex 2.0 network and directed records contain ERCC1 bait with ERCC4 prey in human 293T affinity-purification mass spectrometry. This is co-complex evidence and is consistent with independent heterodimer structures. Network confidence does not turn the screen into a purified binary or isoform-resolved assay. Retain the supported generic binding as non-core. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI supports the tested ERCC4–TACC1 isoform-7 interaction. Reason: The actual HuRI PSI records map Q92889-1 and O75410-7 to the tested clone pair and positive yeast GAL4 assays. Three records represent assay variants for one pair, not three independent papers or independently verified MAPPIT experiments. Preserve the imported TACC1-7 identity and retain the generic interaction as non-core without assigning a cellular mechanism. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: BioPlex 3.0 supports ERCC4–ERCC1 association. Reason: The actual 293T BioPlex 3.0 network and directed records contain ERCC4 bait with ERCC1 prey. The co-complex result agrees with independent heterodimer structures; reused earlier BioPlex data must not be counted as wholly independent replication. Absence from the inspected filtered HCT116 file is not negative biological evidence. Retain generic binding as non-core. |
| GO:0042802 identical protein binding | IPI PMID:22483113 The structure of the XPF-ssDNA complex underscores the disti... | KEEP AS NON CORE | Summary: An isolated human XPF C-terminal fragment forms a homodimer in the structural experiment. Reason: The original PMID:22483113 abstract and official PDB 2KN7 entity/assembly records identify a 67-residue Q92889 fragment, residues 842–908, with two protein chains and two short DNA strands. This supports the fragment self-association assertion, not a physiological full-length XPF homodimer or equivalent behavior of the natural 372-residue product. Retain as non-core; the full original beyond the abstract and deposition was unavailable. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: HPA directly reports human ERCC4 in the nucleoplasm. Reason: The actual HPA target record ENSG00000175595 reports nucleoplasm with both approved ICC/IF antibodies CAB000156 and HPA045828 in A-431, U-251MG and U2OS. The summary reliability is supported. This is source-specific localization evidence rather than an inference from DNA-repair function; it does not resolve natural products individually. Image pixels were not reinterpreted in this review. |
| GO:0016604 nuclear body | IDA GO_REF:0000052 | ACCEPT | Summary: HPA directly reports ERCC4 nuclear-body localization in U2OS cells. Reason: Both approved HPA antibodies CAB000156 and HPA045828 classify the U2OS signal as nucleoplasm and nuclear bodies. This is the operative support for the imported HPA nuclear-body annotation. The inherited PMID:12571280 nuclear-focus quotation remains intact as historical context, but a damage focus is not automatically equivalent to a GO nuclear body. No specific nuclear-body subtype, constitutive localization in every cell line, or natural-product-specific location is asserted. Supporting Evidence: PMID:12571280 FANCA and the known DNA repair protein XPF localize to the same nuclear foci. |
| GO:0006289 nucleotide-excision repair | IDA PMID:22547097 Multiple DNA binding domains mediate the function of the ERC... | ACCEPT | Summary: ERCC4 is the catalytic XPF subunit of the nucleotide-excision repair nuclease. Reason: The accessible PMID:22547097 abstract reports DNA-binding-domain mutants and compares NER with interstrand-crosslink repair; its complete operative original was unavailable. Retain this well-established core process with that access limit and defer to the experimental curator. Independently inspected human XPF knockout/rescue experiments in PMID:32034146 measure UV photolesion removal. No uninspected mutant-specific result is inferred. Supporting Evidence: PMID:22547097 In NER, ERCC1-XPF is recruited to DNA lesions by interaction with XPA and incises the DNA 5' to the lesion. |
| GO:0070522 ERCC4-ERCC1 complex | IPI PMID:16076955 Crystal structure and DNA binding functions of ERCC1, a subu... | ACCEPT | Summary: ERCC4 forms the catalytic subunit of the ERCC4–ERCC1 heterodimer. Reason: The actual PMID:16076955 Results/Methods distinguish full human Sf9-derived enzyme from engineered minimal fragments and describe the C-terminal heterodimer structure and incision assays. This establishes complex membership. The minimal constructs and their tags are experimental reagents, not additional natural isoforms; the natural 372-aa product is not functionally equated to them. Supporting Evidence: PMID:16076955 Human XPF-ERCC1 is a DNA endonuclease that incises a damaged DNA strand on the 5' side of a lesion during nucleotide excision repair |
| GO:0005634 nucleus | EXP PMID:19596235 Mammalian BTBD12/SLX4 assembles a Holliday junction resolvas... | MODIFY | Summary: Human ERCC4 has nucleoplasmic localization within the nucleus. Reason: PMID:19596235 describes nuclear XPF–SLX4 association; its supplementary localization image was not independently inspected. The independently checked Human Protein Atlas antibody evidence supports nucleoplasm, permitting refinement of the broad nucleus term without inventing a more specific damage focus or equating every nuclear-body signal with a repair complex. Proposed replacements: nucleoplasm Supporting Evidence: PMID:19596235 Human SLX4 forms a multiprotein complex with the ERCC4(XPF)-ERCC1, MUS81-EME1, and SLX1 endonucleases |
| GO:0005694 chromosome | EXP PMID:11790111 Contribution of XPF functional domains to the 5' and 3' inci... | ACCEPT | Summary: ERCC4 associates with chromosomal material in the tested human repair preparation. Reason: The inspected PMID:11790111 Methods/Results use human chromatin-associated protein extracts, including normal and XPF-defective cells, to assay incision around a psoralen crosslink. This supports the imported broad chromosome association in that preparation. It does not establish constitutive occupancy across all chromosomes or preferential lesion binding by isolated XPF. |
| GO:0006303 double-strand break repair via nonhomologous end joining | IMP PMID:14690602 ERCC1/XPF removes the 3' overhang from uncapped telomeres an... | KEEP AS NON CORE | Summary: ERCC4 contributes to end joining at experimentally uncapped telomeres. Reason: The actual PMID:14690602 original tests TRF2 inhibition in human XPF-deficient cells and complementary mouse ERCC1-deficient systems. Retained overhangs and reduced fusion support a specialized telomere-processing contribution preceding end joining. XPF is not the ligase, and this experiment does not establish a universal role in ordinary nonhomologous end joining. Supporting Evidence: PMID:14690602 overhang processing is a prerequisite for NHEJ of telomeres. |
| GO:1990599 3' overhang single-stranded DNA endonuclease activity | IMP PMID:14690602 ERCC1/XPF removes the 3' overhang from uncapped telomeres an... | ACCEPT | Summary: ERCC4 contributes to removal of 3′ overhangs from uncapped telomeres. Reason: PMID:14690602 directly measures persistence of telomeric overhangs after TRF2 inhibition in XPF/ERCC1-defective cells. This is an IMP dependency assay, not a purified-enzyme cleavage-site experiment. Retain the curator's contributes_to assignment in the context of independently established junction-nuclease activity, without claiming that this paper alone locates every hydrolyzed bond. Supporting Evidence: PMID:14690602 ERCC1/XPF-deficient cells retained the telomeric overhang after TRF2 inhibition, identifying this nucleotide excision repair endonuclease as the culprit in overhang removal. |
| GO:0006289 nucleotide-excision repair | IDA PMID:10413517 Domain mapping of the DNA binding, endonuclease, and ERCC1 b... | ACCEPT | Summary: The ERCC4 nuclease participates in nucleotide-excision repair. Reason: PMID:10413517 actually measures DNA binding, endonuclease activity and ERCC1 interaction of recombinant human XPF constructs. These support the enzyme's established repair role, although the inspected experiment does not reconstitute the entire NER pathway. Independent human XPF loss/rescue and photolesion-removal work in PMID:32034146 supports the process directly. Retain the core function with the experimental distinction. Supporting Evidence: PMID:10413517 During nucleotide excision repair, one of the two incisions necessary for removal of a broad spectrum of DNA adducts is made by the human XPF/ERCC1 protein complex. |
| GO:0006289 nucleotide-excision repair | IMP PMID:14728600 Defining the function of xeroderma pigmentosum group F prote... | ACCEPT | Summary: ERCC4 participates in nucleotide-excision repair, with a source-specific assay caveat. Reason: The actual PMID:14728600 abstract studies psoralen-crosslink mutagenesis and reports normal dual-incision behavior in XPF-deficient extract under the tested assay. The inherited supporting quotation therefore cannot justify the earlier blanket claim that this experiment demonstrated an NER-incision defect. Its complete operative original was unavailable. Retain the independently established core NER role, directly supported by the inspected human XPF loss/rescue and photolesion-removal experiments in PMID:32034146, while keeping the original paper's distinct crosslink-assay result explicit. Supporting Evidence: PMID:14728600 the XPF nuclear extract is normal in introducing dual incisions during the nucleotide excision repair process. |
| GO:0006289 nucleotide-excision repair | IDA PMID:32034146 Acetylation of XPF by TIP60 facilitates XPF-ERCC1 complex as... | ACCEPT | Summary: Human XPF participates directly in nucleotide-excision repair. Reason: Actual PMID:32034146 Results/Figure 7a–g use XPF-knockout HeLa cells and re-expression controls to measure removal of UV-induced CPDs and 6-4 photoproducts. Wild-type XPF rescues repair, whereas the acetylation-defective K911R construct does not under the tested conditions. This supports the established nuclease contribution to NER, without assigning the subsequent polymerase or ligase reactions to XPF. Supporting Evidence: PMID:32034146 The XPF-ERCC1 heterodimer is a structure-specific endonuclease that is essential for nucleotide excision repair (NER) and interstrand crosslink (ICL) repair in mammalian cells. |
| GO:0034644 cellular response to UV | IDA PMID:32034146 Acetylation of XPF by TIP60 facilitates XPF-ERCC1 complex as... | ACCEPT | Summary: ERCC4 contributes to cellular UV response through photolesion repair. Reason: PMID:32034146 Figures 5 and 7 distinguish UV-regulated XPF acetylation from functional repair: XPF-knockout/rescue experiments measure UV survival and lesion removal in human HeLa cells. The NER contribution, not merely XPF being a TIP60 substrate, supports the cellular-response annotation. This is not a UV-sensor claim. Supporting Evidence: PMID:32034146 TIP60, also known as KAT5, a haplo-insufficient tumor suppressor, directly acetylates XPF at Lys911 following UV irradiation |
| GO:0070522 ERCC4-ERCC1 complex | IDA PMID:32034146 Acetylation of XPF by TIP60 facilitates XPF-ERCC1 complex as... | ACCEPT | Summary: Human XPF is the ERCC4 subunit of the ERCC4–ERCC1 heterodimer. Reason: PMID:32034146 Results/Figure 6 directly measures ERCC1 association with tagged XPF in human cells. K911R removes the UV-induced increase while preserving constitutive interaction; therefore the inherited summary quotation should not be read as making acetylation an absolute prerequisite for every basal heterodimer. The complex membership itself is directly supported. Supporting Evidence: PMID:32034146 this acetylation is required for XPF-ERCC1 complex assembly and subsequent activation. |
| GO:1901255 nucleotide-excision repair involved in interstrand cross-link repair | IDA PMID:32034146 Acetylation of XPF by TIP60 facilitates XPF-ERCC1 complex as... | ACCEPT | Summary: ERCC4 contributes to incision-dependent interstrand-crosslink repair. Reason: PMID:32034146 Figure 7c shows human XPF-knockout HeLa cells are MMC-sensitive and are rescued by wild-type or K911Q XPF, but not K911R. This is a survival assay, not a direct incision-site measurement. Independently, PMID:11790111 actual human chromatin-extract experiments show XPF-dependent incision of crosslinked DNA. Together these support the established repair contribution without equating every ICL pathway with an identical NER-like cut sequence. Supporting Evidence: PMID:32034146 loss of XPF acetylation impairs the damage-induced XPF-ERCC1 interaction, resulting in defects in both NER and ICL repair. |
| GO:0061819 telomeric DNA-containing double minutes formation | IMP PMID:14690602 ERCC1/XPF removes the 3' overhang from uncapped telomeres an... | REMOVE | Summary: ERCC1–XPF deficiency increases telomeric DNA-containing double minutes rather than demonstrating their production by XPF. Reason: GO:0061819 denotes formation of telomeric DNA-containing double minutes. The actual PMID:14690602 Results and Figure 6 compare Ercc1-null mouse fibroblasts with proficient controls and find increased TDMs in deficient cells; Xpc-null cells do not share that increase. The authors' Figure 7 model proposes protective cleavage by ERCC1–XPF that prevents the recombination intermediate producing a TDM. This is evidence against assigning a positive formation step to ERCC4, so remove that process assertion rather than retaining it as partly supported. The human overhang-removal experiments and the mouse TDM phenotype remain distinct, and the proposed protective mechanism does not by itself establish a new negative-regulation annotation. Supporting Evidence: PMID:14690602 ERCC1/XPF-deficient mouse cells had a novel telomere phenotype, characterized by Telomeric DNA-containing Double Minute chromosomes (TDMs). |
| GO:0000781 chromosome, telomeric region | IDA PMID:14690602 ERCC1/XPF removes the 3' overhang from uncapped telomeres an... | KEEP AS NON CORE | Summary: A subset of nuclear ERCC4 associates with telomeric regions. Reason: The inspected PMID:14690602 original and Figure 4 show a small TRF2-associated ERCC1–XPF fraction and detergent-resistant telomeric colocalization in human cells. The telomeric localization is supported but context-specific, not the dominant location of the entire cellular protein pool. Retain this specialized localization as non-core. Supporting Evidence: PMID:14690602 ERCC1/XPF was also identified as a component of the telomeric TRF2 complex. |
| GO:0005515 protein binding | IPI PMID:18812185 Human XPF controls TRF2 and telomere length maintenance thro... | KEEP AS NON CORE | Summary: ERCC4 associates with its ERCC1 partner. Reason: The accessible PMID:18812185 abstract describes XPF–ERCC1-dependent telomere regulation; the detailed original interaction assay was not available. The specific partner relationship is independently established by inspected human complex structures and biochemical experiments in PMID:16076955 and PMID:10413517. Retain supported generic binding as non-core while keeping the paper-specific access limitation explicit. |
| GO:0005515 protein binding | IPI PMID:24012755 SLX4 assembles a telomere maintenance toolkit by bridging mu... | KEEP AS NON CORE | Summary: ERCC4 binds the XPF-interaction region of SLX4. Reason: The inspected PMID:24012755 main Results describe XBR mapping and loss of XPF association after deletion of that SLX4 region. SLX4/TRF2 tethering provides telomeric context; it does not assign SLX1-mediated telomere cutting or every T-SCE phenotype to XPF catalysis. Detailed supplementary construct sequences were not read. Retain the generic interaction as non-core. Supporting Evidence: PMID:24012755 SLX4 assembles a telomere maintenance toolkit by bridging multiple endonucleases with telomeres. |
| GO:0010521 telomerase inhibitor activity | IDA NOT PMID:18812185 Human XPF controls TRF2 and telomere length maintenance thro... | UNDECIDED | Summary: The negated telomerase-inhibitor assertion remains preserved but its exact enzyme-level evidence is unresolved. Reason: The current GO:0010521 definition requires telomerase binding and inhibition. The actual PMID:18812185 abstract separates XPF-dependent TRF2 regulation from telomere-length effects, but does not expose an assay directly testing absence of telomerase inhibition. The full operative original was unavailable. Preserve negated:true and defer this exact IDA assessment rather than converting a length phenotype into a direct inhibitor or non-inhibitor claim. Supporting Evidence: PMID:18812185 XPF-ERCC1 controls TRF2 and telomere length maintenance through two distinctive mechanisms, with the former requiring its nuclease activity. |
| GO:0070522 ERCC4-ERCC1 complex | IDA PMID:14690602 ERCC1/XPF removes the 3' overhang from uncapped telomeres an... | ACCEPT | Summary: ERCC4 is a subunit of the ERCC4–ERCC1 heterodimer. Reason: The inspected PMID:14690602 original, including Figure 4, identifies ERCC1 and XPF together in human TRF2-associated material and uses the established heterodimer in interpreting the telomere phenotype. Independent structural and biochemical evidence confirms the complex. The telomeric fraction is only a subset of the cellular ERCC1–XPF pool. |
| GO:1904357 negative regulation of telomere maintenance via telomere lengthening | IDA PMID:18812185 Human XPF controls TRF2 and telomere length maintenance thro... | KEEP AS NON CORE | Summary: ERCC4 can limit telomere lengthening in the tested cellular contexts. Reason: The actual PMID:18812185 abstract reports XPF overexpression and mutant-rescue effects on telomere length and distinguishes them from nuclease-dependent TRF2 regulation. This supports a specialized length-regulatory role. The full operative source was unavailable, so no particular telomerase-enzyme assay, absolute pathway requirement or precise construct detail is inferred. Supporting Evidence: PMID:18812185 overexpression of XPF induces telomere shortening in XPF-proficient cells whereas XPF complementation suppresses telomere lengthening in XPF-deficient cells. |
| GO:1905765 negative regulation of protection from non-homologous end joining at telomere | IMP PMID:14690602 ERCC1/XPF removes the 3' overhang from uncapped telomeres an... | KEEP AS NON CORE | Summary: ERCC4 helps remove telomeric protection against end joining after TRF2 inhibition. Reason: The actual PMID:14690602 human XPF-deficient-cell experiment links retained 3′ overhangs to reduced telomere fusion after TRF2 inhibition. The current term describes negative regulation of protection from telomeric NHEJ, matching this specialized loss-of-protection context. It is not a claim that XPF globally inhibits chromosome-end protection under normal conditions. Supporting Evidence: PMID:14690602 TRF2 prevents NHEJ at telomeres through protection of the telomeric overhang from ERCC1/XPF. |
| GO:0000723 telomere maintenance | IGI PMID:17055345 XPF with mutations in its conserved nuclease domain is defec... | KEEP AS NON CORE | Summary: ERCC4 influences telomere maintenance in the tested TRF2 genetic context. Reason: The actual PMID:17055345 abstract distinguishes wild-type and nuclease-defective XPF in UV repair and TRF2-associated telomere shortening. The reported restoration of the telomere effect by both variants supports a specialized genetic interaction without making all telomere maintenance dependent on XPF catalysis. The complete operative original was unavailable. Supporting Evidence: PMID:17055345 TRF2-induced telomere shortening is abrogated in human cells deficient in XPF, demonstrating that XPF-ERCC1 is required for TRF2-promoted telomere shortening. |
| GO:0004520 DNA endonuclease activity | IMP PMID:17055345 XPF with mutations in its conserved nuclease domain is defec... | MODIFY | Summary: ERCC4 provides the junction-specific nuclease activity of ERCC1–XPF. Reason: The PMID:17055345 abstract identifies nuclease-defective XPF mutants and separates their repair and telomere phenotypes; the full mutant characterization was unavailable. Independently read human enzyme assays in PMID:14734547 Methods and Figure 3 and PMID:16076955 main Methods/Results establish cleavage of duplex DNA adjacent to a single-stranded junction. Refine the broad catalytic term to GO:0106332 using that positive evidence without claiming to have inspected the unavailable mutant-specific experiments. Proposed replacements: ds/ssDNA junction-specific dsDNA endonuclease activity Supporting Evidence: PMID:17055345 the nuclease-inactive XPF proteins fail to do so, indicating that the nuclease activity of XPF is essential for nucleotide excision repair. |
| GO:0005515 protein binding | IPI PMID:17055345 XPF with mutations in its conserved nuclease domain is defec... | KEEP AS NON CORE | Summary: ERCC4 binds ERCC1 as its nuclease-complex partner. Reason: The complete PMID:17055345 interaction experiment was unavailable. The accessible abstract discusses XPF function and the exact ERCC4–ERCC1 partnership is independently established by inspected human structural and biochemical sources, including PMID:16076955. Retain the supported generic interaction as non-core rather than rejecting it for lack of functional specificity. |
| GO:0006281 DNA repair | IGI PMID:17055345 XPF with mutations in its conserved nuclease domain is defec... | MODIFY | Summary: The supported repair role is nucleotide-excision repair of UV lesions. Reason: The actual PMID:17055345 abstract separates defective UV-lesion repair by nuclease-mutant XPF from a retained telomere-shortening effect. Nucleotide-excision repair is the informative established process for that repair arm; the full original was unavailable, so no more specific genetic assay is claimed. The independent human XPF loss/rescue study PMID:32034146 directly measures photolesion clearance. Proposed replacements: nucleotide-excision repair |
| GO:0034644 cellular response to UV | IGI PMID:17055345 XPF with mutations in its conserved nuclease domain is defec... | ACCEPT | Summary: ERCC4 contributes to cellular UV response through DNA repair. Reason: The accessible PMID:17055345 abstract reports failure of nuclease-defective XPF to restore UV repair. Independently inspected PMID:32034146 human-cell loss/rescue assays measure UV survival and photolesion removal. Retain the cellular-response role, with full access to the former original unavailable; this does not imply that XPF is the UV sensor or a signaling kinase. Supporting Evidence: PMID:17055345 wild type XPF can complement XPF-deficient cells for repair of UV-induced DNA damage |
| GO:0070522 ERCC4-ERCC1 complex | IDA PMID:17055345 XPF with mutations in its conserved nuclease domain is defec... | ACCEPT | Summary: ERCC4 is the catalytic member of the ERCC4–ERCC1 complex. Reason: The full PMID:17055345 experimental complex characterization was unavailable, but the membership is independently established by inspected human structural and biochemical data in PMID:16076955 and PMID:10413517. Retain this correct complex annotation while distinguishing established biology from uninspected paper-specific assay details. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-109955 | ACCEPT | Summary: Nucleoplasmic human ERCC4 is explicitly represented in Formation of ERCC1:XPF heterodimeric complex. Reason: The actual official participant chain is R-HSA-109955 --input--> R-HSA-67445. The terminal entity R-HSA-67445 maps to human UniProtKB:Q92889, residues 1–916, and explicitly has nucleoplasm compartment GO:0005654; the event compartment agrees. This verifies the location assertion for this source event, rather than inferring it from the event title. The participant coordinates describe the canonical source entity and do not establish an identical location or function for the short natural product. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686657 | ACCEPT | Summary: Nucleoplasmic human ERCC4 is explicitly represented in ERCC1:XPF cleaves flaps generated by SSA. Reason: The actual official participant chain is R-HSA-5686657 --input--> R-HSA-9980005 --hasComponent--> R-HSA-109943 --hasComponent--> R-HSA-67445. The terminal entity R-HSA-67445 maps to human UniProtKB:Q92889, residues 1–916, and explicitly has nucleoplasm compartment GO:0005654; the event compartment agrees. This verifies the location assertion for this source event, rather than inferring it from the event title. The participant coordinates describe the canonical source entity and do not establish an identical location or function for the short natural product. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686663 | ACCEPT | Summary: Nucleoplasmic human ERCC4 is explicitly represented in Completion of SSA. Reason: The actual official participant chain is R-HSA-5686663 --output--> R-HSA-109943 --hasComponent--> R-HSA-67445. The terminal entity R-HSA-67445 maps to human UniProtKB:Q92889, residues 1–916, and explicitly has nucleoplasm compartment GO:0005654; the event compartment agrees. This verifies the location assertion for this source event, rather than inferring it from the event title. ERCC4 presence in this repair-completion/ligation context does not assign DNA ligase or polymerase activity to ERCC4. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5690213 | ACCEPT | Summary: Nucleoplasmic human ERCC4 is explicitly represented in DNA polymerases delta, epsilon or kappa bind the GG-NER site. Reason: The actual official participant chain is R-HSA-5690213 --input--> R-HSA-5691059 --hasComponent--> R-HSA-109943 --hasComponent--> R-HSA-67445. The terminal entity R-HSA-67445 maps to human UniProtKB:Q92889, residues 1–916, and explicitly has nucleoplasm compartment GO:0005654; the event compartment agrees. This verifies the location assertion for this source event, rather than inferring it from the event title. The participant coordinates describe the canonical source entity and do not establish an identical location or function for the short natural product. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5690988 | ACCEPT | Summary: Nucleoplasmic human ERCC4 is explicitly represented in 3'-incision of DNA by ERCC5 (XPG) in GG-NER. Reason: The actual official participant chain is R-HSA-5690988 --output--> R-HSA-109943 --hasComponent--> R-HSA-67445. The terminal entity R-HSA-67445 maps to human UniProtKB:Q92889, residues 1–916, and explicitly has nucleoplasm compartment GO:0005654; the event compartment agrees. This verifies the location assertion for this source event, rather than inferring it from the event title. The event concerns ERCC5/XPG incision; the location of the ERCC4 participant does not transfer ERCC5 catalytic specificity to ERCC4. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5690990 | ACCEPT | Summary: Nucleoplasmic human ERCC4 is explicitly represented in 5'- incision of DNA by ERCC1:ERCC4 in GG-NER. Reason: The actual official participant chain is R-HSA-5690990 --input--> R-HSA-5691046 --hasComponent--> R-HSA-109943 --hasComponent--> R-HSA-67445. The terminal entity R-HSA-67445 maps to human UniProtKB:Q92889, residues 1–916, and explicitly has nucleoplasm compartment GO:0005654; the event compartment agrees. This verifies the location assertion for this source event, rather than inferring it from the event title. The participant coordinates describe the canonical source entity and do not establish an identical location or function for the short natural product. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5690991 | ACCEPT | Summary: Nucleoplasmic human ERCC4 is explicitly represented in Binding of ERCC1:ERCC4 (ERCC1:XPF) to pre-incision complex in GG-NER. Reason: The actual official participant chain is R-HSA-5690991 --input--> R-HSA-109943 --hasComponent--> R-HSA-67445. The terminal entity R-HSA-67445 maps to human UniProtKB:Q92889, residues 1–916, and explicitly has nucleoplasm compartment GO:0005654; the event compartment agrees. This verifies the location assertion for this source event, rather than inferring it from the event title. The participant coordinates describe the canonical source entity and do not establish an identical location or function for the short natural product. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6782141 | ACCEPT | Summary: Nucleoplasmic human ERCC4 is explicitly represented in Binding of ERCC1:ERCC4 (ERCC1:XPF) to pre-incision complex in TC-NER. Reason: The actual official participant chain is R-HSA-6782141 --input--> R-HSA-109943 --hasComponent--> R-HSA-67445. The terminal entity R-HSA-67445 maps to human UniProtKB:Q92889, residues 1–916, and explicitly has nucleoplasm compartment GO:0005654; the event compartment agrees. This verifies the location assertion for this source event, rather than inferring it from the event title. The participant coordinates describe the canonical source entity and do not establish an identical location or function for the short natural product. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6782204 | ACCEPT | Summary: Nucleoplasmic human ERCC4 is explicitly represented in 5' incision of damaged DNA strand by ERCC1:ERCC4 in TC-NER. Reason: The actual official participant chain is R-HSA-6782204 --input--> R-HSA-6782142 --hasComponent--> R-HSA-109943 --hasComponent--> R-HSA-67445. The terminal entity R-HSA-67445 maps to human UniProtKB:Q92889, residues 1–916, and explicitly has nucleoplasm compartment GO:0005654; the event compartment agrees. This verifies the location assertion for this source event, rather than inferring it from the event title. The participant coordinates describe the canonical source entity and do not establish an identical location or function for the short natural product. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6782211 | ACCEPT | Summary: Nucleoplasmic human ERCC4 is explicitly represented in DNA polymerases delta, epsilon or kappa bind the TC-NER site. Reason: The actual official participant chain is R-HSA-6782211 --input--> R-HSA-6782205 --hasComponent--> R-HSA-109943 --hasComponent--> R-HSA-67445. The terminal entity R-HSA-67445 maps to human UniProtKB:Q92889, residues 1–916, and explicitly has nucleoplasm compartment GO:0005654; the event compartment agrees. This verifies the location assertion for this source event, rather than inferring it from the event title. The participant coordinates describe the canonical source entity and do not establish an identical location or function for the short natural product. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6782224 | ACCEPT | Summary: Nucleoplasmic human ERCC4 is explicitly represented in 3' incision by ERCC5 (XPG) in TC-NER. Reason: The actual official participant chain is R-HSA-6782224 --output--> R-HSA-109943 --hasComponent--> R-HSA-67445. The terminal entity R-HSA-67445 maps to human UniProtKB:Q92889, residues 1–916, and explicitly has nucleoplasm compartment GO:0005654; the event compartment agrees. This verifies the location assertion for this source event, rather than inferring it from the event title. The event concerns ERCC5/XPG incision; the location of the ERCC4 participant does not transfer ERCC5 catalytic specificity to ERCC4. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785732 | ACCEPT | Summary: Nucleoplasmic human ERCC4 is explicitly represented in DNA nucleases bind monoubiquitinated ID2 complex. Reason: The actual official participant chain is R-HSA-6785732 --input--> R-HSA-109943 --hasComponent--> R-HSA-67445. The terminal entity R-HSA-67445 maps to human UniProtKB:Q92889, residues 1–916, and explicitly has nucleoplasm compartment GO:0005654; the event compartment agrees. This verifies the location assertion for this source event, rather than inferring it from the event title. The ICL pathway involves several coordinated nucleases; this location assertion does not establish that ERCC4 alone performs every incision or fixes their order. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785986 | ACCEPT | Summary: Nucleoplasmic human ERCC4 is explicitly represented in DNA nucleases unhook the interstrand crosslink (ICL). Reason: The actual official participant chain is R-HSA-6785986 --output--> R-HSA-109943 --hasComponent--> R-HSA-67445. The terminal entity R-HSA-67445 maps to human UniProtKB:Q92889, residues 1–916, and explicitly has nucleoplasm compartment GO:0005654; the event compartment agrees. This verifies the location assertion for this source event, rather than inferring it from the event title. The ICL pathway involves several coordinated nucleases; this location assertion does not establish that ERCC4 alone performs every incision or fixes their order. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9980006 | ACCEPT | Summary: Nucleoplasmic human ERCC4 is explicitly represented in ERCC1:XPF binds DNA DSBs with annealed 3' ssDNA overhangs and displaced flaps generated by SSA. Reason: The actual official participant chain is R-HSA-9980006 --input--> R-HSA-109943 --hasComponent--> R-HSA-67445. The terminal entity R-HSA-67445 maps to human UniProtKB:Q92889, residues 1–916, and explicitly has nucleoplasm compartment GO:0005654; the event compartment agrees. This verifies the location assertion for this source event, rather than inferring it from the event title. The participant coordinates describe the canonical source entity and do not establish an identical location or function for the short natural product. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9980021 | ACCEPT | Summary: Nucleoplasmic human ERCC4 is explicitly represented in LIG1 binds SSA sites. Reason: The actual official participant chain is R-HSA-9980021 --input--> R-HSA-9980007 --hasComponent--> R-HSA-109943 --hasComponent--> R-HSA-67445. The terminal entity R-HSA-67445 maps to human UniProtKB:Q92889, residues 1–916, and explicitly has nucleoplasm compartment GO:0005654; the event compartment agrees. This verifies the location assertion for this source event, rather than inferring it from the event title. ERCC4 presence in this repair-completion/ligation context does not assign DNA ligase or polymerase activity to ERCC4. |
| GO:0000110 nucleotide-excision repair factor 1 complex | IDA PMID:10413517 Domain mapping of the DNA binding, endonuclease, and ERCC1 b... | ACCEPT | Summary: ERCC4 belongs to the XPA-containing nucleotide-excision repair factor 1 complex. Reason: The inspected PMID:10413517 S-ERCC1 capture assays map human XPF C-terminal interaction, including residues 667–854, and establish the ERCC1–XPF heterodimer; they do not themselves assay XPA in the captured preparation. The broader membership claim is nevertheless independently supported: current GO:0000110 names human XPA, ERCC1 and ERCC4, the verified PAINT node places the target in this complex, and human Reactome R-HSA-5690991 places ERCC1–ERCC4 in the XPA-containing pre-incision assembly. PMID:32111838 independently establishes the human heterodimer and its XPA-recruitment context, while its larger assembly placement is a model. Accept the same supported NEF1 membership as index 3, preserving the original paper's narrower assay scope and avoiding a claim of a permanent three-subunit assembly. Supporting Evidence: PMID:10413517 the C-terminal 214 residues are capable of binding specifically to ERCC1. |
| GO:0005515 protein binding | IPI PMID:19595721 Coordination of structure-specific nucleases by human SLX4/B... | KEEP AS NON CORE | Summary: Human ERCC4 associates with the SLX4 scaffold. Reason: The actual PMID:19595721 abstract explicitly reports a human SLX4 complex containing XPF–ERCC1 and modulation of nuclease activity. The complete operative original was unavailable. Independent inspected sources PMID:19596235 and PMID:19596236 establish the partner association; retain generic binding as non-core without assigning every SLX4-associated nuclease reaction to XPF. |
| GO:0005515 protein binding | IPI PMID:19595722 Drosophila MUS312 and the vertebrate ortholog BTBD12 interac... | KEEP AS NON CORE | Summary: Human ERCC4 interacts with SLX4 in the tested two-hybrid assay. Reason: Inspected PMID:19595722 sections distinguish human XPF–BTBD12 interaction from the corresponding Drosophila MEI-9/SLX4 genetic comparison. Human XPF G325E loses the tested interaction. This is positive evidence for the named pair, not proof of equivalent behavior for all natural products or a reason to transfer every fly phenotype directly to human XPF. |
| GO:0006281 DNA repair | IMP PMID:19596235 Mammalian BTBD12/SLX4 assembles a Holliday junction resolvas... | MODIFY | Summary: ERCC4 contributes nuclease-dependent repair of UV lesions and interstrand crosslinks. Reason: The actual PMID:19596235 Results, SLX4 is required for resistance to DNA damaging agents that produce interstrand crosslinks or DNA-protein adducts, and Figure 3E–F include human ERCC4 siRNA itself: depletion increases MMC and UV sensitivity. These are ERCC4 experiments, distinct from the inherited supporting quotation about SLX4 depletion, which is retained as complex-level context and does not itself establish the ERCC4 phenotype. Independent human photolesion clearance in PMID:32034146 and crosslinked-DNA incision in PMID:11790111 specify NER and ICL repair. Refine the broad repair assertion to those established routes without transferring SLX1/MUS81 Holliday-junction chemistry or SLX4's DR-GFP result to XPF. Proposed replacements: nucleotide-excision repair interstrand cross-link repair Supporting Evidence: PMID:19596235 Depletion of SLX4 causes sensitivity to mitomycin C and camptothecin and reduces the efficiency of DSB repair in vivo. |
| GO:0000723 telomere maintenance | IMP PMID:14690602 ERCC1/XPF removes the 3' overhang from uncapped telomeres an... | KEEP AS NON CORE | Summary: ERCC4 participates in specialized telomere maintenance responses. Reason: The actual PMID:14690602 original supports telomere-associated XPF, processing after TRF2 inhibition and telomere phenotypes in deficient systems. These support the broad process in a specialized context, not a universal requirement for normal telomere homeostasis. Human XPF experiments are kept distinct from ERCC1-null mouse phenotypes. Supporting Evidence: PMID:14690602 these data reveal an unanticipated involvement of the ERCC1/XPF NER endonuclease in the regulation of telomere integrity |
| GO:0005515 protein binding | IPI PMID:14690602 ERCC1/XPF removes the 3' overhang from uncapped telomeres an... | KEEP AS NON CORE | Summary: ERCC4 associates with TRF2-containing complexes in human cells. Reason: The inspected PMID:14690602 Figure 4 and Results show human TRF2 affinity purification with XPF peptides and reciprocal immunoprecipitation controls. Only a small XPF fraction is recovered with TRF2. These establish association but do not by themselves prove a purified binary interaction; retain generic binding as non-core. |
| GO:0000724 double-strand break repair via homologous recombination | IMP PMID:14728600 Defining the function of xeroderma pigmentosum group F prote... | UNDECIDED | Summary: The source-specific homologous-recombination assertion remains unresolved. Reason: The accessible PMID:14728600 abstract establishes psoralen-crosslink mutagenesis, rescue and extract-assay findings, but does not expose the homologous-recombination experiment underlying this IMP row. The complete original could not be inspected. Preserve the annotation as UNDECIDED rather than inferring an assay from the general XPF-family recombination role or declaring the curator wrong. |
| GO:0003677 DNA binding | IDA PMID:14734547 Physical and functional interaction between the XPF/ERCC1 en... | ACCEPT | Summary: The ERCC1–ERCC4 nuclease has DNA-binding capacity, with ERCC4 contributing to it. Reason: PMID:14734547 uses purified recombinant human ERCC1–XPF and a splayed-arm DNA substrate; its operative direct readout is incision, not an independently quantified equilibrium-binding curve. The imported contributes_to assertion is also supported independently by the human ERCC4 fragment–ssDNA NMR deposition 2KN7 associated with PMID:22483113. Retain broad DNA binding with this source distinction; neither experiment establishes equal function of both natural products. |
| GO:0004520 DNA endonuclease activity | IDA PMID:8797827 Xeroderma pigmentosum group F caused by a defect in a struct... | MODIFY | Summary: ERCC4 contributes junction-specific duplex-DNA nuclease catalysis to the ERCC1–XPF complex. Reason: The PMID:8797827 abstract reports the purified heterodimer's incision on the 5′ side of a lesion; the complete operative original was unavailable. Independently inspected human ERCC1–XPF reactions in PMID:14734547 Methods and Figure 3 and PMID:16076955 main Methods/Results establish junction-specific duplex incision. GO:0106332 therefore refines the established catalytic contribution. The imported contributes_to assertion is preserved, and no unseen experiment or equivalence of shorter natural products is inferred. Proposed replacements: ds/ssDNA junction-specific dsDNA endonuclease activity Supporting Evidence: PMID:8797827 This complex is a structure-specific endonuclease responsible for the 5' incision during repair. |
| GO:0004520 DNA endonuclease activity | IDA PMID:14734547 Physical and functional interaction between the XPF/ERCC1 en... | MODIFY | Summary: Purified human ERCC1–XPF cleaves duplex DNA at a splayed-arm junction. Reason: PMID:14734547 Methods pp. 13634–13635 and Results/Figure 3 measure Mg-containing cleavage of a splayed-arm substrate by recombinant human ERCC1–XPF. Precombining RAD52 with the enzyme stimulates incision, whereas prebinding RAD52 to DNA inhibits it. GO:0106332 captures the duplex/single-strand-junction geometry more precisely than generic DNA endonuclease activity. The experiment does not make XPF an annealase or reconstitute a complete chromosomal recombination pathway. Proposed replacements: ds/ssDNA junction-specific dsDNA endonuclease activity Supporting Evidence: PMID:14734547 Complex formation between hRad52 and XPF/ERCC1 concomitantly stimulates the DNA structure-specific endonuclease activity of XPF/ERCC1 |
| GO:0005515 protein binding | IPI PMID:14734547 Physical and functional interaction between the XPF/ERCC1 en... | KEEP AS NON CORE | Summary: Direct interaction with human RAD52 is supported; retain the generic binding term as non-core. Reason: PMID:14734547 Figure 2 tests purified ERCC1–XPF binding to GST-hRAD52 with an ethidium-bromide control, then uses in-vitro-translated individual subunits to map the interaction to XPF and the RAD52 N-terminal region. This is positive interaction evidence. The generic term lacks functional specificity, but that is not over-annotation under the campaign policy; no independently established adaptor function is inferred merely from binding and nuclease stimulation. |
| GO:0006289 nucleotide-excision repair | IMP PMID:8797827 Xeroderma pigmentosum group F caused by a defect in a struct... | ACCEPT | Summary: ERCC4 is required for the XPF-dependent incision step of nucleotide-excision repair. Reason: The actual PMID:8797827 abstract reports complementation of human XP-F and rodent repair-defective cells and identifies XPF in the incision nuclease. The full operative original was unavailable. The established role is independently supported by inspected modern human XPF knockout/rescue photolesion-removal experiments in PMID:32034146. Supporting Evidence: PMID:8797827 We isolated a human gene homologous to yeast Rad1 and found that it corrects the repair defects of XP group F as well as rodent groups 4 and 11. |
| GO:0032205 negative regulation of telomere maintenance | IMP PMID:17055345 XPF with mutations in its conserved nuclease domain is defec... | KEEP AS NON CORE | Summary: ERCC4 can promote telomere shortening in the studied TRF2 context. Reason: The actual PMID:17055345 abstract reports that both wild-type and nuclease-defective XPF restore the tested TRF2-associated shortening response, unlike their UV-repair behavior. Retain this specialized negative-regulatory annotation as non-core. The full original was unavailable, and the effect is not generalized to every telomere-maintenance setting. Supporting Evidence: PMID:17055345 XPF-ERCC1 is required for TRF2-promoted telomere shortening. |
| GO:0003684 damaged DNA binding | IMP PMID:11790111 Contribution of XPF functional domains to the 5' and 3' inci... | UNDECIDED | Summary: Incision dependence does not by itself resolve a damaged-DNA-binding measurement attributable to XPF. Reason: The actual PMID:11790111 Methods/Results assay incision of a psoralen-crosslinked substrate in human chromatin-associated extracts, using XPF-defective extracts and domain-directed antibody inhibition. They infer domain involvement, but this read scope does not resolve a damaged-DNA-binding measurement attributable to XPF separately from effects on repair-complex assembly and incision. GO:0003684 does not require preferential affinity for damaged over undamaged DNA or an isolated-protein preparation. Retain the imported context as UNDECIDED because the binding evidence itself remains unresolved, without treating lesion recruitment or incision dependence as a specific binding measurement. Supporting Evidence: PMID:11790111 it is involved in production of the 5' incision at the site of a psoralen interstrand cross-link as well as the 3' incision. |
| GO:0003697 single-stranded DNA binding | IDA PMID:10413517 Domain mapping of the DNA binding, endonuclease, and ERCC1 b... | ACCEPT | Summary: Human XPF constructs bind single-stranded DNA. Reason: The actual PMID:10413517 Methods/Results use denatured-DNA cellulose under EDTA/Mg-free conditions; full and N-terminal constructs bind, with different behavior for the tested C-terminal fragments. The N378 reagent spans residues 12–378 and is not the natural 372-residue product. Independent official 2KN7 structural records also show a short human C-terminal fragment bound to ssDNA. The sources need not use identical constructs to support the broad binding function. Supporting Evidence: PMID:10413517 the N-terminal 378 amino acids of XPF are capable of binding and hydrolyzing DNA |
| GO:0004520 DNA endonuclease activity | IDA PMID:10413517 Domain mapping of the DNA binding, endonuclease, and ERCC1 b... | MODIFY | Summary: The established ERCC4 nuclease activity is duplex incision near a single-stranded junction. Reason: The actual PMID:10413517 original demonstrates Mg-dependent plasmid nicking/linearization and renaturation assays with recombinant human XPF constructs. Those measurements establish nuclease capacity but do not alone define junction specificity or validate the older assignment of the catalytic region. Independently inspected PMID:16076955 junction-substrate assays and PMID:32111838 full-length structure/incision experiments support GO:0106332 and distinguish the catalytic nuclease domain from the regulatory helicase-like module. Refine the established function using this combined evidence without relabeling the old construct assay or the natural 372-aa product. Proposed replacements: ds/ssDNA junction-specific dsDNA endonuclease activity Supporting Evidence: PMID:10413517 determined that it is an endonuclease and can bind DNA in the absence of the ERCC1 subunit. |
| GO:0006289 nucleotide-excision repair | IMP PMID:11790111 Contribution of XPF functional domains to the 5' and 3' inci... | ACCEPT | Summary: ERCC4 contributes nuclease activity to the repair system examined with crosslinked DNA. Reason: The inspected PMID:11790111 human extract experiments establish XPF-dependent incision around a psoralen crosslink. Together with independently established human NER loss/rescue evidence, they support XPF's core repair role. Crosslink-associated 3′ incision effects in this extract system do not make XPF the canonical 3′ nuclease of ordinary NER; that role belongs to ERCC5/XPG. Supporting Evidence: PMID:11790111 XPF forms a heterodimeric complex with ERCC1 and is required for the repair of DNA interstrand cross-links. |
| GO:0005515 protein binding | IPI PMID:12571280 Nonerythroid alphaII spectrin is required for recruitment of... | KEEP AS NON CORE | Summary: Human ERCC4 associates with FANCA-containing repair assemblies. Reason: The actual PMID:12571280 abstract explicitly reports human FANCA, alphaII-spectrin and XPF reciprocal co-immunoprecipitation and damage-associated nuclear foci. These support co-complex association. The full operative original was unavailable; no purified binary FANCA–XPF assay is claimed. Retain the generic interaction as non-core. |
| GO:0005634 nucleus | IDA PMID:12571280 Nonerythroid alphaII spectrin is required for recruitment of... | MODIFY | Summary: ERCC4 localizes within the nucleoplasm. Reason: The actual PMID:12571280 abstract describes human damage-associated nuclear XPF foci, while the complete original was unavailable. Independent inspected Human Protein Atlas localization supports nucleoplasm. Refine broad nucleus to that supported location without equating all nuclear signal with a particular repair focus or claiming an unread microscopy control. Proposed replacements: nucleoplasm Supporting Evidence: PMID:12571280 FANCA and the known DNA repair protein XPF localize to the same nuclear foci. |
| GO:0009411 response to UV | IMP PMID:16678501 gamma-H2AX formation in response to interstrand crosslinks r... | ACCEPT | Summary: ERCC4 contributes to the response to UV through DNA repair. Reason: The inspected PMID:16678501 Methods and Results compare human XPF-deficient fibroblasts and rescue under HMT-plus-UVA conditions, with UVA-only controls, and measure gamma-H2AX. This original supports a specialized photocrosslink-damage response; it does not show XPF phosphorylating H2AX. Independently, human XPF knockout/rescue and UV-photolesion clearance in PMID:32034146 Results and Figure 7 establish the broader UV-response claim through repair. Accept that established function consistently with index 14 while preserving the distinct HMT/UVA assay limits; neither experiment implies that XPF senses UV photons. Supporting Evidence: PMID:16678501 XPF is required to form gamma-H2AX and likely double strand breaks in response to interstrand crosslinks in human cells. |
| GO:0005515 protein binding | IPI PMID:9722633 Mapping of interaction domains between human repair proteins... | KEEP AS NON CORE | Summary: The tested human XPF C-terminal region binds ERCC1. Reason: The actual PMID:9722633 abstract maps interacting human C-terminal regions. The XPF coordinates reflect the paper's earlier sequence numbering and must not be silently treated as a separate natural product. The available cached full-text section repeats abstract-level material; no full operative original was read. Independent inspected structures and domain mapping support the partnership, retained as non-core generic binding. |
| GO:0005515 protein binding | IPI PMID:7559382 Purification and characterization of the XPF-ERCC1 complex o... | KEEP AS NON CORE | Summary: Purified human ERCC1 and XPF form an associated repair complex. Reason: The actual PMID:7559382 abstract describes purification of the human HeLa-derived heterodimer and complementation evidence. Its full operative original was unavailable. This agrees with independently inspected human heterodimer structures and biochemical assays. Retain supported generic binding as non-core without inventing unseen purification controls. |
| GO:0000109 nucleotide-excision repair complex | IDA PMID:10644440 Characterization of the mouse Xpf DNA repair gene and differ... | MODIFY | Summary: The established human repair assembly is the ERCC4–ERCC1 heterodimer. Reason: The inspected PMID:10644440 original studies mouse Xpf cloning and spermatogenesis and includes an actual human HeLa chromatographic/immunoblot comparator; its title does not establish absence of human experiments. The inspected sections do not independently demonstrate a human repair-complex assay. Human heterodimer structures and biochemical experiments in independently inspected PMID:32111838 and PMID:16076955 establish the more informative ERCC4–ERCC1 complex. Refine the broad complex term on that independent evidence, while retaining the original IDA source and its access/assay boundary. Proposed replacements: ERCC4-ERCC1 complex Supporting Evidence: PMID:10644440 The human XPF protein, an endonuclease subunit essential for DNA excision repair, may also function in homologous recombination. |
| GO:0006289 nucleotide-excision repair | IDA PMID:10644440 Characterization of the mouse Xpf DNA repair gene and differ... | ACCEPT | Summary: ERCC4 directly participates in nucleotide-excision repair. Reason: Retain this established core process using independently inspected human XPF loss/rescue and photolesion-removal evidence in PMID:32034146. The inspected PMID:10644440 original includes mouse Xpf expression work and a human HeLa protein comparator, but the source-specific human NER assay underlying this IDA row was not identified in those sections. This is not a wrong-gene finding; do not infer a curator error from the mouse-focused title or assign function merely from developmental expression. The imported qualifier is preserved. Supporting Evidence: PMID:10644440 The human XPF protein, an endonuclease subunit essential for DNA excision repair, may also function in homologous recombination. |
| GO:0000014 single-stranded DNA endodeoxyribonuclease activity | IDA PMID:22483113 The structure of the XPF-ssDNA complex underscores the disti... | TOO GENERAL | Summary: Retire the redundant historical broad single-stranded-DNA nuclease proposal. Reason: This retired historical NEW proposal is separate from the 96 current imported contexts. Current GO:1990599, already accepted at indices 1 and 31, is a direct child of GO:0000014, so the broader proposal adds no distinct coverage. TOO_GENERAL records that redundancy; it does not assert that the fragment paper directly establishes arbitrary ssDNA cleavage. PMID:22483113 remains abstract-level plus the official 2KN7 record for a 67-residue XPF fragment, supporting binding/self-association rather than an independent full-length nuclease assay. Preserve retired:true, the original source fields and all inherited quotations; no active NEW assertion is restored. Supporting Evidence: PMID:22483113 Human XPF/ERCC1 is a structure-specific DNA endonuclease that nicks the damaged DNA strand at the 5' end during nucleotide excision repair. PMID:10413517 determined that it is an endonuclease and can bind DNA in the absence of the ERCC1 subunit. |
| GO:0005515 protein binding | IPI PMID:12571280 Nonerythroid alphaII spectrin is required for recruitment of... | KEEP AS NON CORE | Summary: ERCC4 associates with alphaII-spectrin-containing assemblies. Reason: The actual PMID:12571280 abstract explicitly includes human alphaII-spectrin/SPTAN1 with XPF and FANCA in reciprocal co-immunoprecipitation and nuclear-foci observations. This supports the named association, without establishing a purified binary XPF–SPTAN1 interaction. The complete operative original was unavailable; retain the positive generic interaction as non-core. |
| GO:0005515 protein binding | IPI PMID:14690602 ERCC1/XPF removes the 3' overhang from uncapped telomeres an... | KEEP AS NON CORE | Summary: ERCC4 and RAP1 occur in a shared TRF2-associated complex. Reason: The inspected PMID:14690602 original and actual Figure 4A identify RAP1 in the purified TRF2 complex that also contains ERCC1 and XPF. Reciprocal XPF–TRF2 experiments strengthen the complex interpretation but are not a direct purified XPF–RAP1 binary assay. Retain the imported generic association as non-core with this explicit evidence boundary. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: BioPlex 3.0 supports ERCC4–SLX4 co-complex association. Reason: The actual human 293T BioPlex 3.0 network and directed table contain ERCC4 bait with SLX4 prey. This supports co-complex association, independently corroborated by inspected low-throughput human interaction studies. A network score does not establish binary affinity or isoform equivalence; retain the generic binding term as non-core. |
| GO:0001094 TFIID-class transcription factor complex binding | IEA GO_REF:0000107 | UNDECIDED | Summary: The mouse TFIID-binding donor is traceable, but ERCC4-specific binding scope remains unresolved. Reason: Official mouse Q9QZD4 carries IDA GO:0001094 to PMID:22323595, and the human IEA is an orthology transfer of that assertion. Current GO:0001094 concerns binding a general transcription factor belonging to TFIID. In the recovered main original Results/Figure 3A–F, the affinity bait is tagged murine ERCC1 expressed in human HEK293 cells; TAF6/7/10/12 and TBP are recovered, and XPF-associated results are directed partly to SI. The main study supports an ERCC1–XPF/TFIID association model, but does not resolve the ERCC4-specific interaction under this term from the ERCC1-bait complex result. Relevant SI was inaccessible after bounded attempts. Keep the exact source assertion unresolved, not removed as a wrong-gene claim; neither mouse provenance nor an indirect complex assay alone proves it false. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q9QZD4 UNRESOLVED Mouse Ercc4 IDA to PMID:22323595 is present and identity/orthology is consistent. Main original ERCC1-bait affinity purification and the inaccessible SI leave ERCC4-specific TFIID binding unresolved. |
| GO:1990841 promoter-specific chromatin binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse XPF promoter-chromatin occupancy supports the contextual orthology transfer. Reason: Official mouse Q9QZD4 carries IDA GO:1990841 to PMID:22323595. The recovered original Results/Figure 2B directly measure XPF occupancy at liver Igf1, GhR, Dio1 and PrlR promoters, with inactive/upstream controls; Figure 3G–H examines recruitment during adipocyte differentiation. This is chromatin immunoprecipitation evidence for promoter-associated chromatin, which fits the current GO definition without requiring purified sequence-specific DNA binding. Retain a non-core contextual mammalian binding role; the operative tissue and MEF experiments are mouse, not endogenous human ERCC4 assays or evidence for both human natural products. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q9QZD4 SUPPORTS TRANSFER Actual mouse XPF ChIP at selected promoters in PMID:22323595 Figures 2B and 3G–H supports the source assertion; retain the ortholog transfer as contextual, with species and assay limits explicit. |
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Download this section (compressed HTML)Q: Which contacts attributable to human ERCC4 establish binding to damaged DNA separately from repair-complex assembly and incision readouts, and how do they compare with its established duplex-junction contacts?
Q: Does human ERCC4 itself contact TFIID, which subunit and interface are involved, and can that contact be distinguished from ERCC1-mediated or larger-complex association?
Q: Which repair, localization and partner-binding activities are performed by the natural 372-amino-acid ERCC4 product, rather than by full-length XPF or engineered truncations?
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