NBN (nibrin, NBS1) is the regulatory subunit of the MRE11-RAD50-NBN (MRN) complex, the first responder to DNA double-strand breaks (DSBs) in vertebrate cells. NBN has no catalytic or DNA-binding domain of its own. Its N-terminal FHA domain and tandem BRCT domains recognise phosphorylated motifs in MDC1 (CK2-phosphorylated SDTD repeats), RAD17, gamma-H2AX and CDK-phosphorylated CtIP/RBBP8. Its C terminus binds MRE11, holds the complex in the nucleus, and carries an FxF/Y motif that recruits ATM and converts it into an active kinase. Through these contacts NBN tethers MRN to damaged chromatin, activates ATM-dependent checkpoint signalling (intra-S and G2/M arrest through CHK2), and couples break sensing to resection. NBN senses CtIP phosphorylation and directly stimulates the MRE11 endonuclease, which starts end resection for homologous recombination in S/G2. At telomeres, NBN docks on the TRF2 TRFH domain through its YQLSP motif. CDK2 phosphorylation of Ser432 in S/G2 releases it, while PP1-alpha dephosphorylation in G1 restores binding. This phosphorylation state decides whether dysfunctional telomeres are joined by ATM-dependent classical NHEJ (phospho-NBN) or by EXO1/PARP1-dependent alternative NHEJ (TRF2-bound dephospho-NBN). NBN is nuclear, accumulates in IR-induced foci, and also occurs at telomeres, replication forks, PML bodies and, transiently, nucleoli. Loss-of-function variants cause Nijmegen breakage syndrome (microcephaly, immunodeficiency, radiosensitivity, chromosome instability and lymphoid cancer predisposition).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000077 DNA damage checkpoint signaling | IDA PMID:12529385 Critical role for mouse Hus1 in an S-phase DNA damage cell c... | MODIFY | Summary: Mouse Hus1 study in which NBN is used as the comparator for the IR-responsive S-phase checkpoint; NBS1 was not required for the BPDE-induced S-phase checkpoint. Reason: NBN does act in DNA damage checkpoint signaling, but the checkpoint it serves in S phase is the IR-responsive intra-S checkpoint that depends on ATM activation and MDC1-mediated NBN recruitment. The cited paper is about Hus1 and positions NBS1 in the IR-responsive pathway, while showing it is not needed for the BPDE checkpoint. The specific term mitotic intra-S DNA damage checkpoint signaling is supported directly by MDC1-NBS1 disruption experiments. The general row is refined rather than removed. Proposed replacements: mitotic intra-S DNA damage checkpoint signaling Supporting Evidence: PMID:12529385 checkpoint-mediated inhibition of DNA synthesis in response to BPDE did not require NBS1, a component of the IR-responsive S-phase checkpoint pathway PMID:18678890 Disruption of the MDC1-NBS1 interaction results in failure of NBS1 accumulation at DNA double-strand breaks and impairment of intra-S checkpoint activation. |
| GO:0000723 telomere maintenance | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro (Nibrin family) mapping to telomere maintenance. Reason: NBN-deficient patient cells have short telomeres that are rescued only by NBN together with TERT, and NBN acts at telomeres with TRF2 in a cell-cycle-regulated way. The family-level mapping is consistent with this experimental evidence. Supporting Evidence: PMID:11448772 Strikingly, NBS promotes telomere elongation in conjunction with TERT in NBS fibroblasts. These results suggest that NBS is a required accessory protein for telomere extension. |
| GO:0000723 telomere maintenance | IMP PMID:11448772 Rescue of a telomere length defect of Nijmegen breakage synd... | ACCEPT | Summary: NBS patient cells have shortened telomeres; NBN together with TERT restores telomere elongation. Reason: Complementation of NBS fibroblasts shows that NBN is needed for telomerase-mediated telomere extension. This is a direct loss-of-function and rescue result on the human gene. Supporting Evidence: PMID:11448772 We show that blood cells from NBS patients have shortened telomere DNA ends. PMID:11448772 Strikingly, NBS promotes telomere elongation in conjunction with TERT in NBS fibroblasts. |
| GO:0000724 double-strand break repair via homologous recombination | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for double-strand break repair via homologous recombination across the Nibrin/Xrs2 family. Reason: The MRN (MRX in yeast) complex initiates HR at DSBs, and human NBN is required for MRE11 endonuclease activation with phosphorylated CtIP, the first resection step. The IBA node placement matches experimental evidence on the human protein. Supporting Evidence: PMID:27889449 Unlike in yeast, where the Xrs2/NBS1 subunit is dispensable in vitro, NBS1 is absolutely required in the human system. |
| GO:0000724 double-strand break repair via homologous recombination | IDA PMID:22464731 Skp2 E3 ligase integrates ATM activation and homologous reco... | ACCEPT | Summary: SKP2-mediated K63 ubiquitination of NBN promotes ATM recruitment and HR repair. Reason: NBN is a core HR factor. The paper links NBN ubiquitination to ATM activation and HR repair. Supporting Evidence: PMID:22464731 Skp2 interacts with NBS1 and triggers K63-linked ubiquitination of NBS1 upon DSBs, which is critical for the interaction of NBS1 with ATM, thereby facilitating ATM recruitment to the DNA foci for activation. |
| GO:0000724 double-strand break repair via homologous recombination | IDA PMID:23115235 The RING finger protein RNF8 ubiquitinates Nbs1 to promote D... | ACCEPT | Summary: RNF8 ubiquitinates NBN, promoting its stable binding to DSBs and HR-mediated repair. Reason: Supports NBN participation in HR repair of DSBs. Supporting Evidence: PMID:23115235 RNF8-mediated ubiquitination of Nbs1 contributes to the efficient and stable binding of Nbs1 to DSBs and is important for HR-mediated DSB repair. |
| GO:0000724 double-strand break repair via homologous recombination | IDA PMID:27814491 Nbs1 Converts the Human Mre11/Rad50 Nuclease Complex into an... | ACCEPT | Summary: NBN converts MRE11/RAD50 into an endo/exonuclease that processes protein-blocked DNA ends. Reason: Processing of adducted DNA ends by MRN is the initiating step of HR; NBN is required for this activity. Supporting Evidence: PMID:27814491 hMRN catalyzes sequential endonucleolytic and exonucleolytic activities on both 5' and 3' strands of DNA ends containing protein adducts, and that Nbs1, ATP, and adducts are essential for this function. |
| GO:0000724 double-strand break repair via homologous recombination | IDA PMID:27889449 Phosphorylated CtIP Functions as a Co-factor of the MRE11-RA... | ACCEPT | Summary: NBN is absolutely required for MRE11 endonuclease activity with phosphorylated CtIP in the initial resection step of HR. Reason: Direct biochemical evidence that NBN participates in the first step of HR. Supporting Evidence: PMID:27889449 The MRE11 endonuclease in conjunction with RAD50, NBS1, and phosphorylated CtIP preferentially cleaves 5'-terminated DNA strands near DSBs. |
| GO:0000724 double-strand break repair via homologous recombination | IDA PMID:28867292 Single-Molecule Imaging Reveals How Mre11-Rad50-Nbs1 Initiat... | ACCEPT | Summary: Single-molecule imaging of MRN searching for and processing DNA ends and loading EXO1 for long-range resection. Reason: Shows how the MRN complex, of which NBN is an obligate subunit, promotes HR on nucleosome-coated DNA. Supporting Evidence: PMID:28867292 Our results provide a mechanism for how MRN promotes homologous recombination on nucleosome-coated DNA. |
| GO:0000724 double-strand break repair via homologous recombination | IDA PMID:30787182 NBS1 promotes the endonuclease activity of the MRE11-RAD50 c... | ACCEPT | Summary: NBN senses CtIP phosphorylation through its FHA/BRCT domains and activates the MRE11-RAD50 nuclease. Reason: Reconstitution and in vivo evidence that NBN controls the first resection step of HR. Supporting Evidence: PMID:30787182 Using a reconstituted system, we show here that NBS1, through its FHA and BRCT domains, functions as a sensor of CtIP phosphorylation. NBS1 then activates the MRE11-RAD50 nuclease through direct physical interactions with MRE11. |
| GO:0000724 double-strand break repair via homologous recombination | IDA PMID:30952868 Pellino1 regulates reversible ATM activation via NBS1 ubiqui... | ACCEPT | Summary: Pellino1-mediated K63 ubiquitination of NBN promotes ATM feedback activation and HR repair. Reason: Supports NBN participation in HR repair. Supporting Evidence: PMID:30952868 Interaction of Peli1 with phosphorylated histone H2AX enables it to bind to and mediate the formation of K63-linked ubiquitination of NBS1, which subsequently results in feedback activation of ATM and promotes HR repair. |
| GO:0000724 double-strand break repair via homologous recombination | IDA PMID:38961290 NBS1 lactylation is required for efficient DNA repair and ch... | ACCEPT | Summary: NBN K388 lactylation is required for MRN complex formation and HR. Reason: Shows NBN is required for MRN formation and accumulation of HR factors at DSBs. Supporting Evidence: PMID:38961290 Lactylation of NBS1 at lysine 388 (K388) is essential for MRE11-RAD50-NBS1 (MRN) complex formation and the accumulation of HR repair proteins at the sites of DNA double-strand breaks. |
| GO:0000729 DNA double-strand break processing | IDA PMID:16622404 Two-step activation of ATM by DNA and the Mre11-Rad50-Nbs1 c... | ACCEPT | Summary: ATM activation by DNA and MRN; annotated to DNA double-strand break processing. Reason: The cited abstract focuses on MRN tethering DNA and NBN activating ATM, and the full text was not available to us. DSB end processing is nonetheless a well-established NBN function (reconstituted MRN-CtIP resection requires NBN), so the annotation is accepted and the curator's reading of the full text is deferred to. Supporting Evidence: PMID:16622404 The Mre11-Rad50-Nbs1 complex (MRN) facilitates this process by tethering DNA, thereby increasing the local concentration of damaged DNA. PMID:30787182 DNA end resection initiates DNA double-strand break repair by homologous recombination. MRE11-RAD50-NBS1 and phosphorylated CtIP perform the first resection step via MRE11-catalyzed endonucleolytic DNA cleavage. |
| GO:0000729 DNA double-strand break processing | NAS PMID:26512707 ATM-Dependent Phosphorylation of All Three Members of the MR... | ACCEPT | Summary: Review statement that MRN recognises DSBs and initiates processing and signalling. Reason: Consistent with experimental evidence that NBN is required for MRE11-dependent end processing. Supporting Evidence: PMID:26512707 The MRN complex rapidly recognises and locates to DNA DSB where it acts to recruit and assist in ATM activation. PMID:27889449 The MRE11 endonuclease in conjunction with RAD50, NBS1, and phosphorylated CtIP preferentially cleaves 5'-terminated DNA strands near DSBs. |
| GO:0000781 chromosome, telomeric region | HDA PMID:19135898 Purification of proteins associated with specific genomic Lo... | ACCEPT | Summary: PICh proteomics of isolated human telomeric chromatin. Reason: High-throughput telomeric chromatin purification that recovered known telomeric factors; consistent with the TRF2-NBN interaction and NBN telomere localization shown by targeted methods. 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:0000781 chromosome, telomeric region | IDA PMID:10888888 Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TR... | ACCEPT | Summary: NBN associates with TRF2 and telomeres in S phase. Reason: Direct co-immunoprecipitation and localization evidence for NBN at human telomeres. Supporting Evidence: PMID:10888888 NBS1 was associated with TRF2 and telomeres in S phase, but not in G1 or G2. |
| GO:0000781 chromosome, telomeric region | IDA PMID:28216226 NBS1 Phosphorylation Status Dictates Repair Choice of Dysfun... | ACCEPT | Summary: Dephosphorylated NBN docks on the TRF2 TRFH domain and accumulates at functional telomeres; phosphomimetic NBN does not. Reason: Structural and cell-biological evidence for telomere localization of NBN via its YQLSP motif, which is where NBN controls end-joining choice at dysfunctional telomeres. Supporting Evidence: PMID:28216226 The crystal structure of the TRF2-NBS1 complex at 3.0 Γ
resolution shows that the NBS1 429YQLSP433 motif interacts specifically with the TRF2TRFH domain. PMID:28216226 In contrast, Flag-mNBS1S433D and Flag-mNBS1S433E failed to accumulate at functional telomeres (Figures 2B, 2C). |
| GO:0000781 chromosome, telomeric region | IEA GO_REF:0000120 | ACCEPT | Summary: Ensembl ortholog/UniProt subcellular-location transfer from mouse Nbn to telomeric region. Reason: Consistent with direct human evidence for NBN at telomeres. Supporting Evidence: PMID:10888888 NBS1 was associated with TRF2 and telomeres in S phase, but not in G1 or G2. |
| GO:0000781 chromosome, telomeric region | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from mouse Nbn colocalizing with telomeres. Reason: Consistent with human evidence; mouse Nbs1 (S433) is used in the same telomere repair-choice study. Supporting Evidence: PMID:28216226 We identified an evolutionary conserved Cy motif upstream of both hNBS1S432 and mNBS1S433. |
| GO:0001701 in utero embryonic development | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Electronic transfer from mouse Nbn knockout phenotype (embryonic lethality). Reason: Nbn-null mouse embryos die early because NBN is an essential subunit of the MRN DNA repair and replication complex. This is a necessity phenotype of a housekeeping genome-maintenance factor, not evidence that NBN does work specific to embryonic development. The term is kept as an over-annotation rather than removed because the loss-of-function lethality is real. The same action is used for LIG4 GO:0001701; a knockout-lethality term for a housekeeping DNA repair factor is over-annotated unless the gene performs a step of the process. Supporting Evidence: PMID:30657944 since the complete loss of NBS1 is lethal to cells |
| GO:0001832 blastocyst growth | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Electronic transfer from mouse Nbn knockout phenotype (blastocyst growth failure). Reason: As for in utero embryonic development, blastocyst failure in Nbn-null embryos reflects the essential genome-maintenance role of MRN in proliferating cells, not a developmental activity of NBN. Supporting Evidence: PMID:30657944 since the complete loss of NBS1 is lethal to cells |
| GO:0003684 damaged DNA binding | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: PAINT IBA asserting that NBN enables damaged DNA binding. Reason: DNA binding in the MRN complex is provided by MRE11 and RAD50. Human NBN binds gamma-H2AX and phosphorylated mediators rather than damaged DNA, and it is not required for DNA binding by RAD50-containing subcomplexes. NBN contributes to the DNA-end-bound complex, which the IC contributes_to row records, but it does not itself enable damaged DNA binding. Propagation Review Root cause: PROPAGATION BAD Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN000255549 SOURCE WEAK OR INFERRED Nibrin-family ancestral node. Damaged DNA binding of the MRN/MRX complex is carried by MRE11 and RAD50; placing it on the NBN/Xrs2 subunit conflates a complex-level activity with the adaptor subunit. MGI:MGI:1351625 UNRESOLVED Mouse Nbn experimental donor; its own basis was not traced here. Human NBN lacks a DNA-binding region (PMID:12419185). Supporting Evidence: PMID:12419185 NBS1 has no DNA binding region but carries a combination of the fork-head associated (FHA) and the BRCA1 C-terminal domains (BRCT). PMID:28867292 Rad50 binds homoduplex DNA and promotes facilitated diffusion, whereas Mre11 is required for DNA end recognition and nuclease activities. |
| GO:0003684 damaged DNA binding | IC PMID:9590180 Nibrin, a novel DNA double-strand break repair protein, is m... | KEEP AS NON CORE | Summary: Curator inference that NBN contributes to damaged DNA binding as part of the MRN DSB repair complex. Reason: The contributes_to qualifier fits, because MRN binds DNA ends through MRE11 and RAD50, and NBN is a subunit of that complex. NBN's own activities are phosphopeptide binding and enzyme activation, so this is kept as a non-core complex-level contribution. Supporting Evidence: PMID:9590180 The domains found in nibrin and the NBS phenotype suggest that this disorder is caused by defective responses to DNA double-strand breaks. PMID:28867292 Rad50 binds homoduplex DNA and promotes facilitated diffusion, whereas Mre11 is required for DNA end recognition and nuclease activities. |
| GO:0003684 damaged DNA binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl ortholog transfer of damaged DNA binding from mouse Nbn. Reason: Same reasoning as the IBA row; DNA binding in MRN is carried by MRE11 and RAD50, and NBN has no DNA-binding region. Supporting Evidence: PMID:12419185 NBS1 has no DNA binding region but carries a combination of the fork-head associated (FHA) and the BRCA1 C-terminal domains (BRCT). |
| GO:0005515 protein binding | IPI PMID:12419185 NBS1 localizes to gamma-H2AX foci through interaction with t... | MODIFY | Summary: IPI interaction of NBN with H2AX. NBN binds the Ser139-phosphorylated form of H2AX (gamma-H2AX) through its FHA/BRCT region. Reason: Bare protein binding is uninformative. The cited work shows that the H2AX interaction depends on phosphorylation of the partner and on the NBN phosphopeptide-binding FHA/BRCT module, the binding mode through which NBN acts as the MRN adaptor subunit. Replace with phosphorylation-dependent protein binding, a term already carried by NBN from the MDC1 papers. Proposed replacements: phosphorylation-dependent protein binding Supporting Evidence: PMID:12419185 Here, we show that NBS1, the gene product defective in Nijmegen breakage syndrome (NBS), physically interacts with histone, rather than damaged DNA, by direct binding to gamma-H2AX. |
| GO:0005515 protein binding | IPI PMID:12419185 NBS1 localizes to gamma-H2AX foci through interaction with t... | REMOVE | Summary: IPI interaction of NBN with MRE11 (PMID:12419185). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-MRE11 interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:12470659 Recruitment of NBS1 into PML oncogenic domains via interacti... | REMOVE | Summary: IPI interaction of NBN with SP100 (PMID:12470659). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-SP100 interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:12607005 MDC1 is a mediator of the mammalian DNA damage checkpoint. | REMOVE | Summary: IPI interaction of NBN with MDC1 (PMID:12607005). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-MDC1 interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:15916964 ATM-dependent phosphorylation of ATF2 is required for the DN... | REMOVE | Summary: IPI interaction of NBN with ATF2 (PMID:15916964). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-ATF2 interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:16377563 MDC1 directly binds phosphorylated histone H2AX to regulate ... | REMOVE | Summary: IPI interaction of NBN with H2AX (PMID:16377563). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-H2AX interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:17500065 PTIP associates with MLL3- and MLL4-containing histone H3 ly... | REMOVE | Summary: IPI interaction of NBN with MRE11 (PMID:17500065). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-MRE11 interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:17612497 SIRT1 regulates the function of the Nijmegen breakage syndro... | REMOVE | Summary: IPI interaction of NBN with MRE11 (PMID:17612497). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-MRE11 interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:17612497 SIRT1 regulates the function of the Nijmegen breakage syndro... | REMOVE | Summary: IPI interaction of NBN with SIRT1 (PMID:17612497). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-SIRT1 interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:18001824 RNF8 ubiquitylates histones at DNA double-strand breaks and ... | REMOVE | Summary: IPI interaction of NBN with H2AX (PMID:18001824). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-H2AX interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:18001824 RNF8 ubiquitylates histones at DNA double-strand breaks and ... | REMOVE | Summary: IPI interaction of NBN with MDC1 (PMID:18001824). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-MDC1 interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:18001825 RNF8 transduces the DNA-damage signal via histone ubiquityla... | REMOVE | Summary: IPI interaction of NBN with H2AX (PMID:18001825). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-H2AX interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:18583988 Phospho-dependent interactions between NBS1 and MDC1 mediate... | REMOVE | Summary: IPI interaction of NBN with H2AX (PMID:18583988). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-H2AX interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:18583988 Phospho-dependent interactions between NBS1 and MDC1 mediate... | MODIFY | Summary: IPI interaction of NBN with MDC1. NBN binds CK2-phosphorylated SDTD repeats of MDC1 through its FHA and tandem BRCT domains. Reason: Bare protein binding is uninformative. The cited work shows that the MDC1 interaction depends on phosphorylation of the partner and on the NBN phosphopeptide-binding FHA/BRCT module, the binding mode through which NBN acts as the MRN adaptor subunit. Replace with phosphorylation-dependent protein binding, a term already carried by NBN from the MDC1 papers. Proposed replacements: phosphorylation-dependent protein binding Supporting Evidence: PMID:18583988 we establish that this phosphorylation of MDC1 promotes direct, phosphorylation-dependent interactions with NBS1 in a manner that requires the closely apposed FHA and twin BRCT domains in the amino terminus of NBS1. |
| GO:0005515 protein binding | IPI PMID:18678890 MDC1 regulates intra-S-phase checkpoint by targeting NBS1 to... | MODIFY | Summary: IPI interaction of NBN with MDC1. NBN binds the CK2-site-rich region of MDC1 through its phosphopeptide-binding FHA and BRCT domains. Reason: Bare protein binding is uninformative. The cited work shows that the MDC1 interaction depends on phosphorylation of the partner and on the NBN phosphopeptide-binding FHA/BRCT module, the binding mode through which NBN acts as the MRN adaptor subunit. Replace with phosphorylation-dependent protein binding, a term already carried by NBN from the MDC1 papers. Proposed replacements: phosphorylation-dependent protein binding Supporting Evidence: PMID:18678890 The MDC1-NBS1 interaction occurs through a specific region (residues 200-420) of MDC1, which contains multiple consensus casein kinase 2 (CK2) phosphorylation sites. In addition, this interaction requires both the forkhead-associated (FHA) and tandem BRCA1 C-terminal (BRCT) domains of NBS1. |
| GO:0005515 protein binding | IPI PMID:19609304 MRE11-RAD50-NBS1 is a critical regulator of FANCD2 stability... | REMOVE | Summary: IPI interaction of NBN with FANCD2 (PMID:19609304). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-FANCD2 interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:19683501 SOSS complexes participate in the maintenance of genomic sta... | REMOVE | Summary: IPI interaction of NBN with INTS3 (PMID:19683501). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-INTS3 interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:19759395 N terminus of CtIP is critical for homologous recombination-... | REMOVE | Summary: IPI interaction of NBN with RBBP8/CtIP (PMID:19759395). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-RBBP8/CtIP interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:19804756 A supramodular FHA/BRCT-repeat architecture mediates Nbs1 ad... | MODIFY | Summary: IPI interaction of NBN with MDC1. NBN binds diphosphorylated pSer-Asp-pThr-Asp motifs of MDC1. Reason: Bare protein binding is uninformative. The cited work shows that the MDC1 interaction depends on phosphorylation of the partner and on the NBN phosphopeptide-binding FHA/BRCT module, the binding mode through which NBN acts as the MRN adaptor subunit. Replace with phosphorylation-dependent protein binding, a term already carried by NBN from the MDC1 papers. Proposed replacements: phosphorylation-dependent protein binding Supporting Evidence: PMID:19804756 We demonstrate that diphosphorylated pSer-Asp-pThr-Asp motifs, recently identified as multicopy docking sites within Mdc1, are evolutionarily conserved Nbs1 binding targets. |
| GO:0005515 protein binding | IPI PMID:20224574 A divalent FHA/BRCT-binding mechanism couples the MRE11-RAD5... | MODIFY | Summary: IPI interaction of NBN with MDC1. NBN binds phosphorylated MDC1 through both its FHA and BRCT domains. Reason: Bare protein binding is uninformative. The cited work shows that the MDC1 interaction depends on phosphorylation of the partner and on the NBN phosphopeptide-binding FHA/BRCT module, the binding mode through which NBN acts as the MRN adaptor subunit. Replace with phosphorylation-dependent protein binding, a term already carried by NBN from the MDC1 papers. Proposed replacements: phosphorylation-dependent protein binding Supporting Evidence: PMID:20224574 The mechanism of MRN accumulation involves direct binding of the Nijmegen breakage syndrome 1 (NBS1) subunit to phosphorylated mediator of the DNA damage checkpoint 1 (MDC1) |
| GO:0005515 protein binding | IPI PMID:21108945 Acetyltransferase p300 regulates NBS1-mediated DNA damage re... | REMOVE | Summary: IPI interaction of NBN with EP300 (PMID:21108945). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-EP300 interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:22078559 Crystal structure of human Mre11: understanding tumorigenic ... | REMOVE | Summary: IPI interaction of NBN with MRE11 (PMID:22078559). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-MRE11 interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:22157895 Five dysfunctional telomeres predict onset of senescence in ... | REMOVE | Summary: IPI interaction of NBN with H2AX (PMID:22157895). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-H2AX interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:22565321 CDK targeting of NBS1 promotes DNA-end resection, replicatio... | REMOVE | Summary: IPI interaction of NBN with H2AX (PMID:22565321). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-H2AX interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:22565321 CDK targeting of NBS1 promotes DNA-end resection, replicatio... | REMOVE | Summary: IPI interaction of NBN with RBBP8/CtIP (PMID:22565321). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-RBBP8/CtIP interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:24534091 Rad17 recruits the MRE11-RAD50-NBS1 complex to regulate the ... | MODIFY | Summary: IPI interaction of NBN with RAD17. NBN binds RAD17 phosphorylated on Thr622 by ATM. Reason: Bare protein binding is uninformative. The cited work shows that the RAD17 interaction depends on phosphorylation of the partner and on the NBN phosphopeptide-binding FHA/BRCT module, the binding mode through which NBN acts as the MRN adaptor subunit. Replace with phosphorylation-dependent protein binding, a term already carried by NBN from the MDC1 papers. Proposed replacements: phosphorylation-dependent protein binding Supporting Evidence: PMID:24534091 Rad17 is phosphorylated by ATM at a novel Thr622 site resulting in a direct interaction of Rad17 with NBS1, facilitating recruitment of the MRN complex and ATM to the DSB |
| GO:0005515 protein binding | IPI PMID:24651726 ATRX dysfunction induces replication defects in primary mous... | REMOVE | Summary: IPI interaction of NBN with mouse ATRX (PMID:24651726). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-mouse ATRX interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:24981860 Human-chromatin-related protein interactions identify a deme... | REMOVE | Summary: IPI interaction of NBN with MRE11 (PMID:24981860). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-MRE11 interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:25064736 The NBS1-Treacle complex controls ribosomal RNA transcriptio... | REMOVE | Summary: IPI interaction of NBN with TCOF1/Treacle (PMID:25064736). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-TCOF1/Treacle interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:25064736 The NBS1-Treacle complex controls ribosomal RNA transcriptio... | REMOVE | Summary: IPI interaction of NBN with MDC1 (PMID:25064736). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-MDC1 interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:25558984 CtIP tetramer assembly is required for DNA-end resection and... | REMOVE | Summary: IPI interaction of NBN with RBBP8/CtIP (PMID:25558984). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-RBBP8/CtIP interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:25895060 Notch is a direct negative regulator of the DNA-damage respo... | REMOVE | Summary: IPI interaction of NBN with ATM (PMID:25895060). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-ATM interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:26869104 VRK1 phosphorylates and protects NBS1 from ubiquitination an... | REMOVE | Summary: IPI interaction of NBN with VRK1 (PMID:26869104). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-VRK1 interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:27568553 MRNIP/C5orf45 Interacts with the MRN Complex and Contributes... | REMOVE | Summary: IPI interaction of NBN with MRNIP (PMID:27568553). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-MRNIP interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:29656893 DNA Repair Network Analysis Reveals Shieldin as a Key Regula... | REMOVE | Summary: IPI interaction of NBN with MDC1 (PMID:29656893). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-MDC1 interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005515 protein binding | IPI PMID:9590181 The hMre11/hRad50 protein complex and Nijmegen breakage synd... | REMOVE | Summary: IPI interaction of NBN with MRE11 (PMID:9590181). Reason: Generic protein binding is uninformative and is removed under the protein-binding policy. Removal does not dispute the reported NBN-MRE11 interaction; the cited evidence does not establish a more specific molecular function for NBN in this interaction that is not already captured by other rows (Mre11 complex membership, phosphorylation-dependent protein binding, protein serine/threonine kinase activator activity). |
| GO:0005634 nucleus | EXP PMID:10783165 BASC, a super complex of BRCA1-associated proteins involved ... | ACCEPT | Summary: NBN (with BRCA1, BLM and the rest of MRN) forms nuclear foci in cells treated with replication-interfering agents. Reason: Direct experimental evidence for nuclear localization of NBN. The nucleus is the compartment where all of NBN's functions occur; chromatin, DSB-site and telomere sub-locations are captured by other rows. Supporting Evidence: PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005634 nucleus | EXP PMID:26215093 MCM8-9 complex promotes resection of double-strand break end... | ACCEPT | Summary: MCM8-9 interacts with MRN and is needed for its stable association with DSBs; NBN detected in nuclear MCM9 immunoprecipitates. Reason: Consistent with the nuclear location of NBN; UniProt cites this paper for nuclear localization. Supporting Evidence: PMID:26215093 MCM8-9 interacts with MRN and is required for the nuclease activity and stable association of MRN with DSBs. |
| GO:0005634 nucleus | IDA PMID:10888888 Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TR... | ACCEPT | Summary: NBN associates with TRF2 at telomeres and with irradiation-induced nuclear foci. Reason: Direct evidence for nuclear NBN. Supporting Evidence: PMID:10888888 NBS1 was associated with TRF2 and telomeres in S phase, but not in G1 or G2. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic subcellular-location transfer of nucleus. Reason: Consistent with experimental nuclear localization of human NBN. Supporting Evidence: PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005634 nucleus | NAS PMID:18171670 Cell cycle-dependent complex formation of BRCA1.CtIP.MRN is ... | ACCEPT | Summary: NAS statement from the BRCA1-CtIP-MRN complex paper. Reason: NBN is nuclear; the BRCA1-CtIP-MRN complex acts on DSBs in S/G2. Supporting Evidence: PMID:18171670 Here we describe that BRCA1 forms a complex with CtIP and MRN (Mre11/Rad50/Nbs1) in a cell cycle-dependent manner. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Human Protein Atlas immunofluorescence places NBN in the nucleoplasm. Reason: Antibody-based localization agrees with the known nuclear, chromatin-associated location of NBN. Supporting Evidence: PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3785768 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "MRN complex binds DNA double strand breaks". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-3785768 MRN complex binds DNA double strand breaks PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5682018 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "MRN complex bound to shortened telomeres recruits ATM". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5682018 MRN complex bound to shortened telomeres recruits ATM PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5682020 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "MRN complex binds shortened telomeres". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5682020 MRN complex binds shortened telomeres PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5682026 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "MRN bound to shortened telomeres activates ATM". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5682026 MRN bound to shortened telomeres activates ATM PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5682044 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "KAT5 acetylates ATM at DNA DSBs". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5682044 KAT5 acetylates ATM at DNA DSBs PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5682586 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "HERC2 and PIAS4 are recruited to DNA DSBs". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5682586 HERC2 and PIAS4 are recruited to DNA DSBs PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5682588 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "RNF8 binds phosphorylated MDC1 at DNA DSBs". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5682588 RNF8 binds phosphorylated MDC1 at DNA DSBs PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5682598 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "ATM phosphorylates HERC2". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5682598 ATM phosphorylates HERC2 PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5682607 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "PIAS4 SUMOylates HERC2 with SUMO1 at DNA DSBs". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5682607 PIAS4 SUMOylates HERC2 with SUMO1 at DNA DSBs PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5682629 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "HERC2 facilitates UBE2N:UBE2V2 binding to RNF8". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5682629 HERC2 facilitates UBE2N:UBE2V2 binding to RNF8 PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5682858 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "RNF8 and RNF168 ubiquitinate H2AFX". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5682858 RNF8 and RNF168 ubiquitinate H2AFX PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5682863 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "RNF168 binds DNA DSBs". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5682863 RNF168 binds DNA DSBs PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5682965 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "WHSC1 dimethylates histone H4 on lysine K21 at DSBs". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5682965 WHSC1 dimethylates histone H4 on lysine K21 at DSBs PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5682967 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "WHSC1 binds DNA DSBs". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5682967 WHSC1 binds DNA DSBs PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5682983 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "ATM phosphorylates WHSC1". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5682983 ATM phosphorylates WHSC1 PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5682992 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "KDM4A,B bind H4K20Me2". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5682992 KDM4A,B bind H4K20Me2 PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683077 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "RNF8 and RNF168 ubiquitinate KDM4A,B". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5683077 RNF8 and RNF168 ubiquitinate KDM4A,B PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683384 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "UIMC1 and FAM175A bind DNA DSBs". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5683384 UIMC1 and FAM175A bind DNA DSBs PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683385 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "Formation of BRCA1-A complex at DNA DSBs". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5683385 Formation of BRCA1-A complex at DNA DSBs PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683405 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "PPP5C dephosphorylates TP53BP1". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5683405 PPP5C dephosphorylates TP53BP1 PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683425 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "ATM phosphorylates TP53BP1 at DNA DSBs". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5683425 ATM phosphorylates TP53BP1 at DNA DSBs PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683735 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "CHEK2 is recruited to DNA DSBs". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5683735 CHEK2 is recruited to DNA DSBs PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683801 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "CHEK2 phosphorylates BRCA1". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5683801 CHEK2 phosphorylates BRCA1 PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683964 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "ATM phosphorylates EYA1-4". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5683964 ATM phosphorylates EYA1-4 PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683967 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "EYA1-4 dephosphorylates tyrosine Y142 of H2AFX". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5683967 EYA1-4 dephosphorylates tyrosine Y142 of H2AFX PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683986 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "APBB1 and MAPK8 bind diphosphorylated H2AFX". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5683986 APBB1 and MAPK8 bind diphosphorylated H2AFX PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684006 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "KPNA2 translocates NBN to the nucleus". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5684006 KPNA2 translocates NBN to the nucleus PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684052 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "PIAS4 SUMOylates MDC1". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5684052 PIAS4 SUMOylates MDC1 PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684071 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "RNF4 ubiquitinates MDC1". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5684071 RNF4 ubiquitinates MDC1 PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684081 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "MRN complex binds CDK2 and RBBP8". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5684081 MRN complex binds CDK2 and RBBP8 PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684096 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "CDK2 phosphorylates RBBP8". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5684096 CDK2 phosphorylates RBBP8 PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684108 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "BRCA1 binds phosphorylated RBBP8". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5684108 BRCA1 binds phosphorylated RBBP8 PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684140 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "ATM phosphorylates RBBP8". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5684140 ATM phosphorylates RBBP8 PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684875 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "Binding of ATR:ATRIP to RPA at resected DNA DSBs". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5684875 Binding of ATR:ATRIP to RPA at resected DNA DSBs PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684882 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "CHEK1 is recruited to resected DNA DSBs". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5684882 CHEK1 is recruited to resected DNA DSBs PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684887 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "Activation of CHEK1 at resected DNA DSBs". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5684887 Activation of CHEK1 at resected DNA DSBs PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685011 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "ATR activation at DNA DSBs". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5685011 ATR activation at DNA DSBs PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685156 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "ATR phosphorylates RPA2". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5685156 ATR phosphorylates RPA2 PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685341 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "BCDX2 complex stabilizes RAD51 filament". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5685341 BCDX2 complex stabilizes RAD51 filament PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685838 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "CX3 complex binds D-loop structures". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5685838 CX3 complex binds D-loop structures PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685985 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "EXO1 or DNA2 in complex with BLM or WRN binds initially resected DNA DSBs along with BRIP1 recruitment". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5685985 EXO1 or DNA2 in complex with BLM or WRN binds initially resected DNA DSBs along with BRIP1 recruitment PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685994 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "Long-range resection of DNA DSBs by EXO1 or DNA2". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5685994 Long-range resection of DNA DSBs by EXO1 or DNA2 PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686410 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "BLM mediates dissolution of double Holliday junction". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5686410 BLM mediates dissolution of double Holliday junction PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686440 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "MUS81:EME1,EME2 cleaves D-loop". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5686440 MUS81:EME1,EME2 cleaves D-loop PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686469 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "Resolution of D-loops cleaved by MUS81:EME1 or MUS81:EME2". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5686469 Resolution of D-loops cleaved by MUS81:EME1 or MUS81:EME2 PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686483 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "Resolution of Holliday junctions cleaved by GEN1 or SLX1A:SLX4:MUS81:EME1,(MUS81:EME2)". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5686483 Resolution of Holliday junctions cleaved by GEN1 or SLX1A:SLX4:MUS81:EME1,(MUS81:EME2) PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686642 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "RAD52 promotes single strand annealing at resected DNA DSBs". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5686642 RAD52 promotes single strand annealing at resected DNA DSBs PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686657 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "ERCC1:XPF cleaves flaps generated by SSA". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5686657 ERCC1:XPF cleaves flaps generated by SSA PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686663 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "Completion of SSA". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5686663 Completion of SSA PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686685 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "RIF1 and PAX1IP bind TP53BP1 at DNA DSBs". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5686685 RIF1 and PAX1IP bind TP53BP1 at DNA DSBs PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686704 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "Activated ATM phosphorylates DCLRE1C". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5686704 Activated ATM phosphorylates DCLRE1C PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686900 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "TP53BP1 recruits DCLRE1C to ATM". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5686900 TP53BP1 recruits DCLRE1C to ATM PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5687464 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "MRN and RBBP8 resect DNA DSBs in MMEJ". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5687464 MRN and RBBP8 resect DNA DSBs in MMEJ PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5687465 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "MRN complex binds RBBP8". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5687465 MRN complex binds RBBP8 PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5687484 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "PARP1 or PARP2, FEN1 and POLQ are recruited to MMEJ site". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5687484 PARP1 or PARP2, FEN1 and POLQ are recruited to MMEJ site PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5687640 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "POLQ extends annealed 3'-ssDNA overhangs in MMEJ". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5687640 POLQ extends annealed 3'-ssDNA overhangs in MMEJ PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5687653 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "PARP1,PARP2 dimers bound to MMEJ sites autoPARylate". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5687653 PARP1,PARP2 dimers bound to MMEJ sites autoPARylate PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5687664 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "FEN1 cleaves displaced ssDNA flaps during MMEJ". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5687664 FEN1 cleaves displaced ssDNA flaps during MMEJ PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5687673 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "MRN recruits LIG3:XRCC1 to MMEJ sites". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5687673 MRN recruits LIG3:XRCC1 to MMEJ sites PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5687675 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "LIG3 ligates remaining SSBs in MMEJ". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5687675 LIG3 ligates remaining SSBs in MMEJ PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693536 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "ATM phosphorylates MDC1". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5693536 ATM phosphorylates MDC1 PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693539 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "Ligation of DNA and formation of Holliday structures following repair synthesis". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5693539 Ligation of DNA and formation of Holliday structures following repair synthesis PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693540 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "MRN activates ATM". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5693540 MRN activates ATM PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693542 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "Association of RPA complexes with ssDNA at resected DNA DSBs". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5693542 Association of RPA complexes with ssDNA at resected DNA DSBs PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693549 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "ATM phosphorylates histone H2AFX on S139 at DNA DSBs". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5693549 ATM phosphorylates histone H2AFX on S139 at DNA DSBs PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693551 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "Phosphorylation of BRCA1-A complex at multiple sites by ATM". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5693551 Phosphorylation of BRCA1-A complex at multiple sites by ATM PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693561 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "RAD51 binds BRCA2 at resected DNA DSBs". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5693561 RAD51 binds BRCA2 at resected DNA DSBs PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693564 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "Association of RAD51 with RAD52:DNA double-strand break ends". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5693564 Association of RAD51 with RAD52:DNA double-strand break ends PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693566 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "TP53BP1 associates with H4K20Me2 at DNA DSBs". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5693566 TP53BP1 associates with H4K20Me2 at DNA DSBs PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693580 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "Association of RAD52 with the RPA complex at resected DNA DSBs". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5693580 Association of RAD52 with the RPA complex at resected DNA DSBs PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693583 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "MDC1 associates with gamma-H2AFX at nuclear foci". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5693583 MDC1 associates with gamma-H2AFX at nuclear foci PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693584 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "Cleavage of Holliday junctions by GEN1 or SLX1A:SLX4:MUS81:EME1,(MUS81:EME2)". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5693584 Cleavage of Holliday junctions by GEN1 or SLX1A:SLX4:MUS81:EME1,(MUS81:EME2) PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693589 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "D-loop dissociation and strand annealing". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5693589 D-loop dissociation and strand annealing PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693593 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "D-loop extension by DNA polymerases". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5693593 D-loop extension by DNA polymerases PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693598 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "ATM phosphorylates NBN". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5693598 ATM phosphorylates NBN PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693599 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "Association of Ku heterodimer with ends of DNA double-strand break". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5693599 Association of Ku heterodimer with ends of DNA double-strand break PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693602 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "ATM recognizes H2AFX-Nucleosomes". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5693602 ATM recognizes H2AFX-Nucleosomes PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693608 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "Initial resection of double-strand break ends". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5693608 Initial resection of double-strand break ends PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693612 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "MRN complex bound to DNA ends recruits ATM". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5693612 MRN complex bound to DNA ends recruits ATM PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693620 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "D-loop formation mediated by PALB2, BRCA2 and RAD51". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-5693620 D-loop formation mediated by PALB2, BRCA2 and RAD51 PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6792712 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "KAT5 acetylates ATM at shortened telomeres". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-6792712 KAT5 acetylates ATM at shortened telomeres PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6799332 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "ATR phosphorylates TP53". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-6799332 ATR phosphorylates TP53 PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-69891 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "Phosphorylation and activation of CHEK2 by ATM". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-69891 Phosphorylation and activation of CHEK2 by ATM PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-75174 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "Association of RAD50:MRE11A complex with NBN (NBS1) via MRE11A interaction". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-75174 Association of RAD50:MRE11A complex with NBN (NBS1) via MRE11A interaction PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9701199 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "Defective D-loop formation mediated by PALB2, BRCA2 and RAD51 due to loss-of-function of BRCA1 in PALB2 binding". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-9701199 Defective D-loop formation mediated by PALB2, BRCA2 and RAD51 due to loss-of-function of BRCA1 in PALB2 binding PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9704330 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "Defective D-loop formation mediated by PALB2, BRCA2 and RAD51 due to loss-of-function of PALB2 in BRCA1 binding". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-9704330 Defective D-loop formation mediated by PALB2, BRCA2 and RAD51 due to loss-of-function of PALB2 in BRCA1 binding PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9704408 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "Defective D-loop formation mediated by PALB2, BRCA2 and RAD51 due to loss-of-function of PALB2 in binding to BRCA2/RAD51/RAD51C". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-9704408 Defective D-loop formation mediated by PALB2, BRCA2 and RAD51 due to loss-of-function of PALB2 in binding to BRCA2/RAD51/RAD51C PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9709571 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "BRCA2 mutants with BRC defects or a defect in the C-terminal RAD51 binding site do not bind RAD51". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-9709571 BRCA2 mutants with BRC defects or a defect in the C-terminal RAD51 binding site do not bind RAD51 PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9709601 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "Defective recruitment of BRCA2 and RAD51 due to loss of BRCA2 function in PALB2 binding". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-9709601 Defective recruitment of BRCA2 and RAD51 due to loss of BRCA2 function in PALB2 binding PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9853389 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "FIGNL1 binds RAD51". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-9853389 FIGNL1 binds RAD51 PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9980006 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "ERCC1:XPF binds DNA DSBs with annealed 3' ssDNA overhangs and displaced flaps generated by SSA". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-9980006 ERCC1:XPF binds DNA DSBs with annealed 3' ssDNA overhangs and displaced flaps generated by SSA PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9980021 | ACCEPT | Summary: Reactome places NBN, as part of the MRN complex or as a DNA damage response participant, in the nucleoplasm for the event "LIG1 binds SSA sites". Reason: NBN is a nuclear protein that acts on DNA double-strand breaks and telomeres; nuclear localization is shown experimentally (UniProt cites PubMed:10783165 and PubMed:26215093) and by HPA immunofluorescence (GO_REF:0000052 row). The Reactome event places the MRN-containing entity in the nucleoplasm, which is consistent with this. The location is accurate at the compartment level; the finer DSB-site and telomere locations are captured by other rows. Supporting Evidence: Reactome:R-HSA-9980021 LIG1 binds SSA sites PMID:10783165 We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. |
| GO:0005657 replication fork | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic transfer of replication fork from mouse Nbn. Reason: The MRN complex colocalizes with PCNA at replication forks throughout S phase, and NBN S432 phosphorylation is needed to restart stalled forks. NBN is present at forks, but its defining activity is at DSBs, so the location is kept as non-core. Supporting Evidence: PMID:11486038 The Mre11 complex colocalized with PCNA at replication forks throughout S phase, both prior to and coincident with the appearance of nascent DNA. PMID:22565321 Impairment of NBS1 phosphorylation not only negatively affects DSB repair by HR, but also prevents resumption of DNA replication after replication-fork stalling. |
| GO:0005694 chromosome | EXP PMID:12419185 NBS1 localizes to gamma-H2AX foci through interaction with t... | ACCEPT | Summary: NBN localizes to gamma-H2AX foci on damaged chromatin. Reason: Experimental evidence that NBN is chromatin-bound at damage sites. Supporting Evidence: PMID:12419185 Here, we show that NBS1, the gene product defective in Nijmegen breakage syndrome (NBS), physically interacts with histone, rather than damaged DNA, by direct binding to gamma-H2AX. |
| GO:0005694 chromosome | EXP PMID:18411307 Phosphorylation of SDT repeats in the MDC1 N terminus trigge... | ACCEPT | Summary: Phosphorylated MDC1 SDT repeats retain NBN on DSB-flanking chromatin. Reason: Direct evidence of NBN chromatin retention. Supporting Evidence: PMID:18411307 DNA double-strand breaks (DSBs) trigger accumulation of the MRE11-RAD50-Nijmegen breakage syndrome 1 (NBS1 [MRN]) complex, whose retention on the DSB-flanking chromatin facilitates survival. |
| GO:0005694 chromosome | EXP PMID:18582474 Structure of a second BRCT domain identified in the nijmegen... | ACCEPT | Summary: NBN BRCT2 is essential for MDC1-dependent relocalization of NBN to DNA damage sites. Reason: Experimental chromatin localization of NBN at damage sites. Supporting Evidence: PMID:18582474 Structure-based single point mutations in human Nbs1 were evaluated in vivo and revealed that BRCT2 is essential for an MDC1-dependent relocalization of Nbs1 to DNA damage sites |
| GO:0005694 chromosome | EXP PMID:18583988 Phospho-dependent interactions between NBS1 and MDC1 mediate... | ACCEPT | Summary: CK2-targeted MDC1 motifs mediate NBN association with chromatin flanking unrepaired DSBs. Reason: Experimental chromatin localization of NBN. Supporting Evidence: PMID:18583988 we show that these CK2-targeted motifs in MDC1 are required to mediate NBS1 association with chromatin-flanking sites of unrepaired DSBs. |
| GO:0005694 chromosome | EXP PMID:18678890 MDC1 regulates intra-S-phase checkpoint by targeting NBS1 to... | ACCEPT | Summary: MDC1 targets NBN to DSB sites. Reason: Experimental chromatin localization of NBN. Supporting Evidence: PMID:18678890 Here we report that MDC1 directly binds to NBS1 and targets NBS1 to the sites of DNA damage. |
| GO:0005694 chromosome | EXP PMID:19338747 Histone H2AX participates the DNA damage-induced ATM activat... | ACCEPT | Summary: NBN is recruited to damaged chromatin in a gamma-H2AX-dependent manner. Reason: Experimental chromatin localization of NBN. Supporting Evidence: PMID:19338747 we show that ATM as well as NBS1 is recruited to damaged-chromatin in a gamma-H2AX-dependent manner. |
| GO:0005694 chromosome | EXP PMID:23115235 The RING finger protein RNF8 ubiquitinates Nbs1 to promote D... | ACCEPT | Summary: RNF8 ubiquitination promotes binding of NBN to DSB-containing chromatin. Reason: Live-cell evidence for NBN on damaged chromatin. Supporting Evidence: PMID:23115235 RNF8 and its ubiquitination activity are important for promoting optimal binding of Nbs1 to DSB-containing chromatin. |
| GO:0005694 chromosome | EXP PMID:24534091 Rad17 recruits the MRE11-RAD50-NBS1 complex to regulate the ... | ACCEPT | Summary: Phosphorylated RAD17 recruits MRN early to DSBs. Reason: Experimental chromatin localization of NBN at DSBs. Supporting Evidence: PMID:24534091 Rad17 is phosphorylated by ATM at a novel Thr622 site resulting in a direct interaction of Rad17 with NBS1, facilitating recruitment of the MRN complex and ATM to the DSB |
| GO:0005694 chromosome | EXP PMID:26215093 MCM8-9 complex promotes resection of double-strand break end... | ACCEPT | Summary: MCM8-9 is required for stable association of MRN with DSBs. Reason: Supports chromatin localization of the MRN complex including NBN. Supporting Evidence: PMID:26215093 MCM8-9 interacts with MRN and is required for the nuclease activity and stable association of MRN with DSBs. |
| GO:0005694 chromosome | EXP PMID:26438602 Acetylation of Histone H2AX at Lys 5 by the TIP60 Histone Ac... | ACCEPT | Summary: TIP60 acetylation of H2AX K5 controls NBN turnover on damaged chromatin. Reason: Experimental chromatin localization of NBN. Supporting Evidence: PMID:26438602 The loss of H2AX acetylation at Lys 5 by TIP60 in cells disturbed the accumulation of NBS1 at sites of DNA damage. |
| GO:0005694 chromosome | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location (Chromosome) mapped to GO. Reason: Consistent with many experimental papers placing NBN on damaged chromatin and telomeres. Supporting Evidence: PMID:18583988 we show that these CK2-targeted motifs in MDC1 are required to mediate NBS1 association with chromatin-flanking sites of unrepaired DSBs. |
| GO:0005730 nucleolus | IDA PMID:10888888 Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TR... | KEEP AS NON CORE | Summary: Nucleolar localization, annotated from the TRF2-MRN telomere paper. Reason: The cited abstract does not mention the nucleolus and the full text was not available to us, so the curator's reading is deferred to. Independent evidence shows that NBN is transiently recruited into nucleoli by TCOF1/Treacle after DNA damage, where it contributes to rRNA silencing. This is a real but condition-specific location, kept as non-core. Supporting Evidence: PMID:25064736 This is associated with transient recruitment of the Nijmegen breakage syndrome protein 1 (NBS1), a central regulator of DNA damage responses, into the nucleoli. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5684006 | KEEP AS NON CORE | Summary: Reactome event "KPNA2 translocates NBN to the nucleus" places NBN in the cytosol before KPNA2-mediated nuclear import. Reason: The cytosolic NBN pool is a newly synthesised, pre-import state: KPNA2 binds the NBN nuclear localization signal (residues 461-467) and imports it so that MRN complexes can form in the nucleus. The location is real but transient and is not where NBN acts, so it is kept as non-core. Supporting Evidence: Reactome:R-HSA-5684006 KPNA2 translocates NBN to the nucleus Reactome:R-HSA-5684006 KPNA2 facilitates the translocation of NBN (NBS1) to the nucleus, thereby making NBN available for the formation of MRN complexes in response to DNA double-strand breaks (DSBs) |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5684008 | KEEP AS NON CORE | Summary: Reactome event "NBN binds KPNA2" places NBN in the cytosol before KPNA2-mediated nuclear import. Reason: The cytosolic NBN pool is a newly synthesised, pre-import state: KPNA2 binds the NBN nuclear localization signal (residues 461-467) and imports it so that MRN complexes can form in the nucleus. The location is real but transient and is not where NBN acts, so it is kept as non-core. Supporting Evidence: Reactome:R-HSA-5684008 NBN binds KPNA2 Reactome:R-HSA-5684006 KPNA2 facilitates the translocation of NBN (NBS1) to the nucleus, thereby making NBN available for the formation of MRN complexes in response to DNA double-strand breaks (DSBs) |
| GO:0006281 DNA repair | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro family mapping to DNA repair. Reason: Broad but correct; NBN is an MRN subunit required for DSB repair. Supporting Evidence: PMID:9590181 The implication of hMre11/hRad50/p95 protein complex in NBS reveals a direct molecular link between DSB repair and cell cycle checkpoint functions. |
| GO:0006302 double-strand break repair | IDA PMID:9590181 The hMre11/hRad50 protein complex and Nijmegen breakage synd... | ACCEPT | Summary: Identification of p95/NBS1 as a component of the hMre11/hRad50 DSB repair complex; NBS cells fail to form hMre11/hRad50 IR-induced foci. Reason: Founding evidence that NBN is a subunit of the DSB repair complex and is required for its damage-induced foci. Supporting Evidence: PMID:9590181 p95 deficiency in these cells completely abrogates the formation of hMre11/hRad50 ionizing radiation-induced foci. |
| GO:0006302 double-strand break repair | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro mapping to double-strand break repair. Reason: Correct; consistent with experimental evidence. Supporting Evidence: PMID:9590181 We have isolated the gene encoding p95, a member of the hMre11/hRad50 double-strand break repair complex. |
| GO:0006974 DNA damage response | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro mapping to DNA damage response. Reason: Broad but correct; NBN is a central DNA damage response factor. Supporting Evidence: PMID:26869104 NBS1 participates in the early detection of DNA damage and functions as a platform for the recruitment and assembly of components that are sequentially required for the repair process. |
| GO:0007095 mitotic G2 DNA damage checkpoint signaling | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for mitotic G2 DNA damage checkpoint signaling. Reason: Human NBN is required for ATM-dependent CHK2 activation and the IR-induced block to mitotic entry, and the NBN FHA domain is needed for G2/M checkpoint activation. The family-level assertion is supported. Supporting Evidence: PMID:11438675 the impaired Chk2 function in NBS cells correlates with the inability, unlike normal cells, to stop entry into mitosis immediately after irradiation PMID:20224574 only mutation in the FHA domain, but not in the BRCT domains, yields a G2/M checkpoint defect |
| GO:0007095 mitotic G2 DNA damage checkpoint signaling | IDA PMID:11438675 Chk2 activation dependence on Nbs1 after DNA damage. | ACCEPT | Summary: NBS cells cannot activate CHK2 after IR and fail to stop mitotic entry; rescued by wild-type but not S343A NBN. Reason: Direct loss-of-function and complementation evidence. Supporting Evidence: PMID:11438675 Interestingly, the impaired Chk2 function in NBS cells correlates with the inability, unlike normal cells, to stop entry into mitosis immediately after irradiation, a checkpoint abnormality that can be corrected by introduction of the wild-type but not the S343A mutant form of Nbs1. |
| GO:0007095 mitotic G2 DNA damage checkpoint signaling | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro mapping to mitotic G2 DNA damage checkpoint signaling. Reason: Consistent with experimental evidence on human NBN. Supporting Evidence: PMID:11438675 Here we show that the ATM-dependent activation of Chk2 by gamma- radiation requires Nbs1 |
| GO:0016605 PML body | IDA PMID:10811102 Nijmegen breakage syndrome disease protein and MRE11 at PML ... | KEEP AS NON CORE | Summary: A portion of NBN and MRE11 concentrates in PML nuclear bodies in undamaged cells. Reason: Real localization, but PML bodies are a storage or ALT-associated location rather than where NBN performs its core damage-response activities. Supporting Evidence: PMID:10811102 Here we demonstrate that in the absence of DNA damage, a portion of p95 and MRE11 is concentrated in PML nuclear bodies (NBs); MRE11 localization to the NBs is p95-dependent. |
| GO:0016605 PML body | IDA PMID:12470659 Recruitment of NBS1 into PML oncogenic domains via interacti... | KEEP AS NON CORE | Summary: SP100 recruits NBN into PML oncogenic domains. Reason: Real localization mediated by SP100; peripheral to the core function. Supporting Evidence: PMID:12470659 These results indicate that NBS1 is recruited into PODs via interaction with SP100 protein. |
| GO:0016605 PML body | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Electronic transfer of PML body localization. Reason: Consistent with the experimental human rows; non-core. Supporting Evidence: PMID:12470659 These results indicate that NBS1 is recruited into PODs via interaction with SP100 protein. |
| GO:0030174 regulation of DNA-templated DNA replication initiation | TAS PMID:9590181 The hMre11/hRad50 protein complex and Nijmegen breakage synd... | MARK AS OVER ANNOTATED | Summary: TAS for regulation of DNA-templated DNA replication initiation, cited to the p95/NBS1 cloning paper. Reason: The cited paper establishes NBN as part of the MRE11/RAD50 DSB repair complex and links it to cell cycle checkpoints; it does not address replication origin firing. NBN-deficient cells show radioresistant DNA synthesis because the intra-S checkpoint fails, which is better captured by the intra-S checkpoint term. A direct role of NBN in regulating replication initiation is not established. Supporting Evidence: PMID:9590181 The implication of hMre11/hRad50/p95 protein complex in NBS reveals a direct molecular link between DSB repair and cell cycle checkpoint functions. |
| GO:0030330 DNA damage response, signal transduction by p53 class mediator | TAS PMID:9590181 The hMre11/hRad50 protein complex and Nijmegen breakage synd... | KEEP AS NON CORE | Summary: TAS for p53-mediated DNA damage signal transduction, cited to the p95/NBS1 cloning paper. Reason: NBN contributes to p53 signalling indirectly, as the MRN subunit that recruits and activates ATM, which then phosphorylates p53. The role is upstream activation of the kinase rather than a step in p53 signal transduction itself, so it is kept as non-core. Supporting Evidence: PMID:15790808 Inactive ATM dimers were activated in vitro with DNA in the presence of MRN, leading to phosphorylation of the downstream cellular targets p53 and Chk2. |
| GO:0030870 Mre11 complex | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for Mre11 complex membership across the Nibrin/Xrs2 family. Reason: NBN (Xrs2 in budding yeast, Nbs1 in fission yeast) is the third obligate subunit of the MRE11-RAD50 complex. The IBA node placement matches extensive human evidence. Supporting Evidence: PMID:9590181 We have isolated the gene encoding p95, a member of the hMre11/hRad50 double-strand break repair complex. |
| GO:0030870 Mre11 complex | IDA PMID:10888888 Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TR... | ACCEPT | Summary: NBN co-purifies with RAD50 and MRE11 in TRF2 immunocomplexes. Reason: Direct evidence that NBN is the third component of the MRE11 complex. Supporting Evidence: PMID:10888888 Protein blotting showed that a small fraction of RAD50, MRE11 and the third component of the MRE11 double-strand break (DSB) repair complex, the Nijmegen breakage syndrome protein (NBS1), is associated with TRF2. |
| GO:0030870 Mre11 complex | IDA PMID:19151086 RAD50 and NBS1 form a stable complex functional in DNA bindi... | ACCEPT | Summary: Purified RAD50-NBS1 and RAD50-MRE11-NBS1 complexes characterised by scanning force microscopy. Reason: Biochemical reconstitution of complexes containing NBN. Supporting Evidence: PMID:19151086 These data show that in vitro, R, M and N form a variety of stable complexes with variable subunit composition and stoichiometry |
| GO:0030870 Mre11 complex | IDA PMID:27889449 Phosphorylated CtIP Functions as a Co-factor of the MRE11-RA... | ACCEPT | Summary: Reconstituted MRN with phosphorylated CtIP; NBN is required for MRE11 endonuclease activity. Reason: Purified human MRN complex containing NBN. Supporting Evidence: PMID:27889449 Unlike in yeast, where the Xrs2/NBS1 subunit is dispensable in vitro, NBS1 is absolutely required in the human system. |
| GO:0030870 Mre11 complex | IDA PMID:28867292 Single-Molecule Imaging Reveals How Mre11-Rad50-Nbs1 Initiat... | ACCEPT | Summary: Single-molecule imaging of purified MRN. Reason: Purified human MRN complex containing NBN. Supporting Evidence: PMID:28867292 Here, we use high-throughput single-molecule microscopy to show that MRN searches for free DNA ends by one-dimensional facilitated diffusion, even on nucleosome-coated DNA. |
| GO:0030870 Mre11 complex | IDA PMID:30787182 NBS1 promotes the endonuclease activity of the MRE11-RAD50 c... | ACCEPT | Summary: NBN activates MRE11-RAD50 through direct physical contact with MRE11 in the reconstituted complex. Reason: Direct evidence for NBN in the MRE11 complex. Supporting Evidence: PMID:30787182 NBS1 then activates the MRE11-RAD50 nuclease through direct physical interactions with MRE11. |
| GO:0030870 Mre11 complex | IDA PMID:38961290 NBS1 lactylation is required for efficient DNA repair and ch... | ACCEPT | Summary: NBN K388 lactylation is essential for MRN complex formation. Reason: Direct evidence for NBN as an MRN subunit. Supporting Evidence: PMID:38961290 Lactylation of NBS1 at lysine 388 (K388) is essential for MRE11-RAD50-NBS1 (MRN) complex formation |
| GO:0030870 Mre11 complex | IDA PMID:9590181 The hMre11/hRad50 protein complex and Nijmegen breakage synd... | ACCEPT | Summary: p95/NBS1 identified as a member of the hMre11/hRad50 complex. Reason: Founding evidence for NBN in the MRE11 complex. Supporting Evidence: PMID:9590181 We have isolated the gene encoding p95, a member of the hMre11/hRad50 double-strand break repair complex. |
| GO:0030870 Mre11 complex | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic transfer of Mre11 complex membership. Reason: Consistent with experimental evidence. Supporting Evidence: PMID:9590181 We have isolated the gene encoding p95, a member of the hMre11/hRad50 double-strand break repair complex. |
| GO:0030870 Mre11 complex | IPI PMID:31147924 Purification and Biophysical Characterization of the Mre11-R... | ACCEPT | Summary: Methods paper on purification of the human MRN complex. Reason: Purification of the complex containing NBN. Supporting Evidence: PMID:31147924 In human cells, MRN is a >500 kDa multifunctional complex that encodes DNA binding, ATPase, and both endonuclease and exonuclease activities. |
| GO:0030870 Mre11 complex | TAS PMID:27918544 A balance between elongation and trimming regulates telomere... | ACCEPT | Summary: TAS for Mre11 complex from the hESC telomere trimming paper. Reason: The paper describes Nbs1 as a member of the MRN complex. Supporting Evidence: PMID:27918544 We then focused on Nbs1, a member of the Mre11/Rad50/Nbs1 complex and potential candidate involved in T-Circle formation |
| GO:0031848 protection from non-homologous end joining at telomere | IDA PMID:28216226 NBS1 Phosphorylation Status Dictates Repair Choice of Dysfun... | KEEP AS NON CORE | Summary: Dephosphorylated NBN docks on the TRF2 TRFH domain, which likely sequesters MRN from functional telomere ends and prevents fusions in G1. Reason: TRF2 is the primary agent of protection; NBN contributes the YQLSP docking motif that lets TRF2 hold MRN away from the ends, and phosphorylation of S432 by CDK2 releases it. NBN participates through its own binding activity, so the annotation stands, but the protective work is led by TRF2 and the authors state the sequestration role as likely, so it is kept as non-core. Supporting Evidence: PMID:28216226 binding of NBS1 to the TRF2TRFH domain likely also serve to sequester the MRN complex away from telomere ends, preventing the activation of aberrant repair (fusions) in G1. |
| GO:0031848 protection from non-homologous end joining at telomere | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic transfer from mouse Nbn of protection from NHEJ at telomere. Reason: Same reasoning as the IDA row; mouse NBS1 S433 behaves like human S432 in the same study. Supporting Evidence: PMID:28216226 Our data suggest that de-phosphorylation of mNBS1S433 by PP1-Ξ± promotes NBS1-TRF2 interaction in G1, while phosphorylation by CDK2 in S/G2 dissociates NBS1S432 from TRF2. |
| GO:0031860 telomeric 3' overhang formation | IMP PMID:16374507 The involvement of the Mre11/Rad50/Nbs1 complex in the gener... | KEEP AS NON CORE | Summary: MRN knockdown transiently shortens telomeric G-overhangs in telomerase-positive cells. Reason: Loss-of-function evidence for a telomerase-dependent role of MRN in G-overhang generation. The effect is transient and the authors suggest it acts through telomerase recruitment, so it is non-core. Supporting Evidence: PMID:16374507 Reduction of MRN resulted in a transient shortening of G-overhang length in telomerase-positive cells. |
| GO:0032206 positive regulation of telomere maintenance | IMP PMID:16374507 The involvement of the Mre11/Rad50/Nbs1 complex in the gener... | KEEP AS NON CORE | Summary: MRN may be involved in recruitment or action of telomerase at telomere ends. Reason: Consistent with NBN being required for telomerase-mediated telomere extension in NBS fibroblasts. Regulatory and context-specific, so non-core. Supporting Evidence: PMID:16374507 which suggested that the MRN complex might be involved in the recruitment or action of telomerase. PMID:11448772 These results suggest that NBS is a required accessory protein for telomere extension. |
| GO:0035825 homologous recombination | NAS PMID:30657944 CtIP-BRCA1 complex and MRE11 maintain replication forks in t... | ACCEPT | Summary: NAS for homologous recombination from a study of CtIP-BRCA1 and MRE11 in chain-terminating nucleoside analog tolerance. Reason: The paper shows NBS1 is required to remove incorporated chain terminators from replicating DNA, a nuclease-dependent end-processing role shared with HR. HR participation by NBN is well established experimentally. Supporting Evidence: PMID:30657944 indicating that NBS1 is also required for removing CTNAs from the replicative DNA PMID:23115235 RNF8-mediated ubiquitination of Nbs1 contributes to the efficient and stable binding of Nbs1 to DSBs and is important for HR-mediated DSB repair. |
| GO:0035861 site of double-strand break | IDA PMID:15916964 ATM-dependent phosphorylation of ATF2 is required for the DN... | ACCEPT | Summary: ATM-phosphorylated ATF2 colocalizes with gamma-H2AX and MRN at IR-induced foci. Reason: Localization of MRN components including NBN to IR-induced DSB foci. Supporting Evidence: PMID:15916964 results in its rapid colocalization with gamma-H2AX and MRN components into IR-induced foci (IRIF). |
| GO:0035861 site of double-strand break | IDA PMID:16622404 Two-step activation of ATM by DNA and the Mre11-Rad50-Nbs1 c... | ACCEPT | Summary: MRN and the NBN ATM-binding domain activate ATM at damaged DNA. Reason: NBN acts at DSBs to activate ATM. Supporting Evidence: PMID:16622404 First, dimeric ATM is recruited to damaged DNA and dissociates into monomers. |
| GO:0035861 site of double-strand break | IDA PMID:18411307 Phosphorylation of SDT repeats in the MDC1 N terminus trigge... | ACCEPT | Summary: MDC1 SDT repeats retain NBN at DSBs. Reason: Direct evidence of NBN accumulation at DSB sites. Supporting Evidence: PMID:18411307 disruption of the SDT-associated phosphoacceptor sites prevented the retention of NBS1 at DSBs. |
| GO:0035861 site of double-strand break | IDA PMID:18582474 Structure of a second BRCT domain identified in the nijmegen... | ACCEPT | Summary: NBN relocalizes to DNA damage sites in an MDC1- and BRCT2-dependent manner. Reason: Direct evidence of NBN at DSB sites. Supporting Evidence: PMID:18582474 BRCT2 is essential for an MDC1-dependent relocalization of Nbs1 to DNA damage sites |
| GO:0035861 site of double-strand break | IDA PMID:18583988 Phospho-dependent interactions between NBS1 and MDC1 mediate... | ACCEPT | Summary: NBN associates with chromatin flanking unrepaired DSBs. Reason: Direct evidence of NBN at DSB sites. Supporting Evidence: PMID:18583988 we show that these CK2-targeted motifs in MDC1 are required to mediate NBS1 association with chromatin-flanking sites of unrepaired DSBs. |
| GO:0035861 site of double-strand break | IDA PMID:18678890 MDC1 regulates intra-S-phase checkpoint by targeting NBS1 to... | ACCEPT | Summary: MDC1 targets NBN to DSBs. Reason: Direct evidence of NBN at DSB sites. Supporting Evidence: PMID:18678890 Disruption of the MDC1-NBS1 interaction results in failure of NBS1 accumulation at DNA double-strand breaks |
| GO:0035861 site of double-strand break | IDA PMID:19338747 Histone H2AX participates the DNA damage-induced ATM activat... | ACCEPT | Summary: NBN recruited to damaged chromatin dependent on gamma-H2AX. Reason: Direct evidence of NBN at DSB sites. Supporting Evidence: PMID:19338747 we show that ATM as well as NBS1 is recruited to damaged-chromatin in a gamma-H2AX-dependent manner. |
| GO:0035861 site of double-strand break | IDA PMID:23115235 The RING finger protein RNF8 ubiquitinates Nbs1 to promote D... | ACCEPT | Summary: RNF8 promotes stable binding of NBN to DSBs. Reason: Direct evidence of NBN at DSB sites. Supporting Evidence: PMID:23115235 RNF8-mediated ubiquitination of Nbs1 contributes to the efficient and stable binding of Nbs1 to DSBs |
| GO:0035861 site of double-strand break | IDA PMID:24534091 Rad17 recruits the MRE11-RAD50-NBS1 complex to regulate the ... | ACCEPT | Summary: RAD17 recruits MRN to DSBs early, independently of MDC1. Reason: Direct evidence of NBN at DSB sites. Supporting Evidence: PMID:24534091 Rad17, a replication checkpoint protein, is required for the early recruitment of the MRN complex to the DSB site that is independent of MDC1 and contributes to ATM activation. |
| GO:0035861 site of double-strand break | IDA PMID:28867292 Single-Molecule Imaging Reveals How Mre11-Rad50-Nbs1 Initiat... | ACCEPT | Summary: MRN finds and processes free DNA ends in single-molecule assays. Reason: MRN, including NBN, acts at DNA ends. Supporting Evidence: PMID:28867292 MRN gains access to occluded DNA ends by removing Ku or other DNA adducts via an Mre11-dependent nucleolytic reaction. |
| GO:0035861 site of double-strand break | IDA PMID:38961290 NBS1 lactylation is required for efficient DNA repair and ch... | ACCEPT | Summary: NBN lactylation promotes accumulation of HR proteins at DSBs. Reason: Supports NBN action at DSB sites. Supporting Evidence: PMID:38961290 the accumulation of HR repair proteins at the sites of DNA double-strand breaks |
| GO:0042393 histone binding | IPI PMID:19338747 Histone H2AX participates the DNA damage-induced ATM activat... | KEEP AS NON CORE | Summary: NBN interacts with gamma-H2AX. Reason: NBN can bind phosphorylated H2AX through its FHA/BRCT region, and its recruitment to damaged chromatin depends on gamma-H2AX. However, MDC1 is the principal gamma-H2AX reader, and most NBN retention at DSBs goes through phosphorylated MDC1. Direct histone binding is therefore real but secondary to the MDC1 route. Supporting Evidence: PMID:19338747 we show that ATM as well as NBS1 is recruited to damaged-chromatin in a gamma-H2AX-dependent manner. PMID:12419185 a recombinant FHA/BRCT domain alone can bind to recombinant gamma-H2AX PMID:16377563 These data provide compelling evidence that the MDC1/NFBD1 BRCT repeat domain is the major mediator of gammaH2AX recognition following DNA damage. |
| GO:0042405 nuclear inclusion body | IDA PMID:12447371 The mismatch repair system is required for S-phase checkpoin... | UNDECIDED | Summary: Nuclear inclusion body localization from a paper on mismatch repair and S-phase checkpoint activation. Reason: The abstract says that ATM-mediated NBS1 phosphorylation occurs independently of mismatch repair, but it does not describe NBN localization, and the full text was not available. Nuclear inclusion body usually denotes protein aggregates. The annotation may describe damage-induced foci, but this cannot be verified. Supporting Evidence: PMID:12447371 Catalytic activation of ATM and ATM-mediated phosphorylation of the protein NBS1 (also called nibrin) occurred independently of mismatch repair. |
| GO:0043247 telomere maintenance in response to DNA damage | IDA PMID:28216226 NBS1 Phosphorylation Status Dictates Repair Choice of Dysfun... | ACCEPT | Summary: The S432 phosphorylation state of NBN selects classical versus alternative NHEJ at dysfunctional telomeres. Reason: NBN does part of the work in both repair routes. Phospho-NBN binds MRE11 and activates ATM for classical NHEJ at telomeres lacking TRF2, while TRF2-bound dephospho-NBN promotes alternative NHEJ at telomeres lacking POT1-TPP1. This is the process the CDK2/PP1-alpha switch controls. Supporting Evidence: PMID:28216226 Classical-NHEJ-mediated repair of telomeres lacking TRF2 requires phosphorylated NBS1S432 to activate ATM, while interaction of de-phosphorylated NBS1S432 with TRF2 promotes alternative-NHEJ repair of telomeres lacking POT1-TPP1. PMID:28216226 Our data reveal that phosphorylation of NBS1S432 functions as a switch to dictate dysfunctional telomere repair pathway choice. |
| GO:0043247 telomere maintenance in response to DNA damage | IEA GO_REF:0000107 | ACCEPT | Summary: Electronic transfer from mouse Nbn of telomere maintenance in response to DNA damage. Reason: Mouse NBS1 S433 behaves as human S432 in the same study. Supporting Evidence: PMID:28216226 Phosphorylation of mNBS1S433 and C-NHEJ fusions require CDK2, since fusions are completely abolished in Cdk2β/β MEFs |
| GO:0043539 protein serine/threonine kinase activator activity | IDA PMID:16622404 Two-step activation of ATM by DNA and the Mre11-Rad50-Nbs1 c... | ACCEPT | Summary: The NBN ATM-binding domain is required and sufficient to convert ATM monomers into active kinase. Reason: A direct biochemical activity of NBN, and its defining signalling function. The C-terminal FxF/Y motif binds ATM and promotes ATM recruitment and activation. Supporting Evidence: PMID:16622404 Second, the ATM-binding domain of Nbs1 is required and sufficient to convert unphosphorylated ATM monomers into enzymatically active monomers in the absence of DNA. |
| GO:0044818 mitotic G2/M transition checkpoint | NAS PMID:22369660 BRCA1 tumor suppressor network: focusing on its tail. | ACCEPT | Summary: NAS for mitotic G2/M transition checkpoint from a review of the BRCA1 BRCT network. Reason: NBN is required for the IR-induced G2/M checkpoint through ATM-CHK2 activation and its FHA domain. The review describes the BRCA1-C complex (CtIP-MRN) in checkpoint and repair. Supporting Evidence: PMID:22369660 The BRCA1-C complex consists of CtIP and the MRN (Mre11/Rad50/Nbs1) complex. PMID:20224574 only mutation in the FHA domain, but not in the BRCT domains, yields a G2/M checkpoint defect |
| GO:0045190 isotype switching | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic transfer from mouse Nbn of isotype switching. Reason: MRN contributes to class-switch recombination, which proceeds through programmed DSBs in B cells. This is a tissue-specific use of the general DSB repair and signalling activity of NBN, so it is non-core. Supporting Evidence: PMID:31147924 The Mre11-Rad50-Nbs1 (MRN) complex coordinates the repair of DNA double-strand breaks, replication fork restart, meiosis, class-switch recombination, and telomere maintenance. |
| GO:0051726 regulation of cell cycle | TAS PMID:9590181 The hMre11/hRad50 protein complex and Nijmegen breakage synd... | TOO GENERAL | Summary: TAS for regulation of cell cycle, cited to the p95/NBS1 cloning paper. Reason: True but uninformative; the specific checkpoint roles of NBN (mitotic G2 DNA damage checkpoint signaling, intra-S checkpoint) are asserted elsewhere in this review. Supporting Evidence: PMID:9590181 The implication of hMre11/hRad50/p95 protein complex in NBS reveals a direct molecular link between DSB repair and cell cycle checkpoint functions. |
| GO:0062176 R-loop processing | IDA PMID:31537797 MRE11-RAD50-NBS1 promotes Fanconi Anemia R-loop suppression ... | KEEP AS NON CORE | Summary: MRN suppresses R-loops at transcription-replication conflicts through a non-nucleolytic MRE11 function in the Fanconi anemia pathway. Reason: Experimental evidence that MRN, including NBN, acts in R-loop suppression. NBN's specific contribution is not resolved and the role is peripheral to DSB signalling and repair, so it is non-core. Supporting Evidence: PMID:31537797 While MRN has been shown to promote R-loops at DNA double-strand breaks, we show that it suppresses R-loops and associated DNA damage at transcription-replication conflicts. |
| GO:0070533 BRCA1-C complex | IPI PMID:16391231 Multifactorial contributions to an acute DNA damage response... | KEEP AS NON CORE | Summary: DNA damage-dependent BRCA1/BARD1 super complexes containing MRN. Reason: The BRCA1-C complex is BRCA1 with CtIP and MRN. NBN is a member through its binding of phosphorylated CtIP. Membership is real but is a downstream assembly of MRN rather than NBN's primary complex. Supporting Evidence: PMID:16391231 Following exposure to genotoxic stress, DNA damage-specific interactions were observed between BRCA1/BARD1 and the DNA damage-response proteins, TopBP1 and Mre11/Rad50/NBS1. PMID:22369660 The BRCA1-C complex consists of CtIP and the MRN (Mre11/Rad50/Nbs1) complex. |
| GO:0070534 protein K63-linked ubiquitination | ISS GO_REF:0000024 | REMOVE | Summary: ISS from PELI1 (Q96FA3) for protein K63-linked ubiquitination. Reason: PELI1 is the E3 ligase that catalyses K63-linked ubiquitination; NBN is its substrate. A substrate does not perform the ubiquitination process. Transfer by sequence similarity from an E3 ligase to an unrelated adaptor protein is an over-propagation, since NBN shares no ligase domain with PELI1. Supporting Evidence: PMID:30952868 Interaction of Peli1 with phosphorylated histone H2AX enables it to bind to and mediate the formation of K63-linked ubiquitination of NBS1 |
| GO:0090656 t-circle formation | IMP PMID:27918544 A balance between elongation and trimming regulates telomere... | KEEP AS NON CORE | Summary: Nbs1 knockdown reduces T-circle formation in human embryonic stem cells. Reason: Loss-of-function evidence that NBN contributes to T-circle formation in telomere trimming in hESCs. This is a cell-type-specific telomere length control role, so non-core. Supporting Evidence: PMID:27918544 We demonstrate that XRCC3 and Nbs1 mediate telomere attrition by catalyzing the formation of T-circles and C-rich overhangs. |
| GO:0090737 telomere maintenance via telomere trimming | IGI PMID:27918544 A balance between elongation and trimming regulates telomere... | KEEP AS NON CORE | Summary: Genetic interaction with XRCC3 in telomere trimming in hESCs. Reason: Same study; non-core telomere length control role. Supporting Evidence: PMID:27918544 telomere trimming, which is controlled by XRCC3 and Nbs1, homologous recombination proteins that generate single-stranded C-rich telomeric DNA and double-stranded telomeric circular DNA (T-circles), respectively. |
| GO:0097681 double-strand break repair via alternative nonhomologous end joining | IDA PMID:28216226 NBS1 Phosphorylation Status Dictates Repair Choice of Dysfun... | KEEP AS NON CORE | Summary: TRF2-bound dephosphorylated NBN promotes alternative NHEJ at telomeres lacking POT1-TPP1. Reason: Experimental evidence that NBN participates in alternative NHEJ, but it is shown only at telomeres lacking POT1-TPP1, where TRF2-docked NBN recruits EXO1 for resection. The general telomere damage-response role is accepted on GO:0043247; this route-specific term is kept as non-core. Supporting Evidence: PMID:28216226 Classical-NHEJ-mediated repair of telomeres lacking TRF2 requires phosphorylated NBS1S432 to activate ATM, while interaction of de-phosphorylated NBS1S432 with TRF2 promotes alternative-NHEJ repair of telomeres lacking POT1-TPP1. |
| GO:0097681 double-strand break repair via alternative nonhomologous end joining | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic transfer from mouse Nbn of alternative NHEJ. Reason: Same as the IDA row. Supporting Evidence: PMID:28216226 De-phosphorylation of NBS1S432/3 by PP1-Ξ± inhibits fusions, while PNUTS inhibits PP1-Ξ± to promote fusions. |
| GO:0098687 chromosomal region | NAS PMID:26512707 ATM-Dependent Phosphorylation of All Three Members of the MR... | ACCEPT | Summary: NAS for chromosomal region from a review of ATM and MRN. Reason: NBN localizes to DSB-flanking chromatin and telomeres, both chromosomal regions. Supporting Evidence: PMID:26512707 The MRN complex rapidly recognises and locates to DNA DSB where it acts to recruit and assist in ATM activation. |
| GO:0110025 DNA strand resection involved in replication fork processing | IDA PMID:27814491 Nbs1 Converts the Human Mre11/Rad50 Nuclease Complex into an... | KEEP AS NON CORE | Summary: Reconstituted MRN processes protein-blocked DNA ends; annotated to DNA strand resection involved in replication fork processing. Reason: MRN does process DNA at stalled replication forks, and NBN S432 phosphorylation is needed for replication restart after fork stalling, so the claim is kept for the gene as a non-core role. The cited paper itself uses DSB-end substrates, which support DNA double-strand break processing (GO:0000729, accepted on other rows) rather than fork processing; the fork-specific claim rests on the fork restart evidence. Supporting Evidence: PMID:27814491 hMRN catalyzes sequential endonucleolytic and exonucleolytic activities on both 5' and 3' strands of DNA ends containing protein adducts, and that Nbs1, ATP, and adducts are essential for this function. PMID:22565321 Impairment of NBS1 phosphorylation not only negatively affects DSB repair by HR, but also prevents resumption of DNA replication after replication-fork stalling. |
| GO:0110025 DNA strand resection involved in replication fork processing | IDA PMID:27889449 Phosphorylated CtIP Functions as a Co-factor of the MRE11-RA... | KEEP AS NON CORE | Summary: MRN with phosphorylated CtIP cleaves 5'-terminated strands near DSBs. Reason: MRN does process DNA at stalled replication forks, and NBN S432 phosphorylation is needed for replication restart after fork stalling, so the claim is kept for the gene as a non-core role. The cited paper itself uses DSB-end substrates, which support DNA double-strand break processing (GO:0000729, accepted on other rows) rather than fork processing; the fork-specific claim rests on the fork restart evidence. Supporting Evidence: PMID:27889449 Our results define the initial step of HR that is particularly relevant for the processing of DSBs bearing protein blocks. PMID:22565321 Impairment of NBS1 phosphorylation not only negatively affects DSB repair by HR, but also prevents resumption of DNA replication after replication-fork stalling. |
| GO:0110025 DNA strand resection involved in replication fork processing | IDA PMID:30787182 NBS1 promotes the endonuclease activity of the MRE11-RAD50 c... | KEEP AS NON CORE | Summary: NBN senses CtIP phosphorylation and activates MRE11-RAD50 for the first resection step. Reason: MRN does process DNA at stalled replication forks, and NBN S432 phosphorylation is needed for replication restart after fork stalling, so the claim is kept for the gene as a non-core role. The cited paper itself uses DSB-end substrates, which support DNA double-strand break processing (GO:0000729, accepted on other rows) rather than fork processing; the fork-specific claim rests on the fork restart evidence. Supporting Evidence: PMID:30787182 DNA end resection initiates DNA double-strand break repair by homologous recombination. MRE11-RAD50-NBS1 and phosphorylated CtIP perform the first resection step via MRE11-catalyzed endonucleolytic DNA cleavage. PMID:22565321 Impairment of NBS1 phosphorylation not only negatively affects DSB repair by HR, but also prevents resumption of DNA replication after replication-fork stalling. |
| GO:0110025 DNA strand resection involved in replication fork processing | NAS PMID:29709199 The MRE11-RAD50-NBS1 Complex Conducts the Orchestration of D... | KEEP AS NON CORE | Summary: NAS from a review describing MRN as a conductor of responses at DSBs and stalled replication forks. Reason: MRN acts at stalled forks, and NBN S432 phosphorylation is needed for replication restart after fork stalling. The fork-specific resection role is real but secondary to DSB processing, so it is kept as non-core. Supporting Evidence: PMID:29709199 Within its network assemblies, MRN is the core conductor for the initial and sustained responses to DNA double-strand breaks, stalled replication forks, dysfunctional telomeres, and viral DNA infection. PMID:22565321 Impairment of NBS1 phosphorylation not only negatively affects DSB repair by HR, but also prevents resumption of DNA replication after replication-fork stalling. |
| GO:0140031 phosphorylation-dependent protein binding | IDA PMID:18411307 Phosphorylation of SDT repeats in the MDC1 N terminus trigge... | ACCEPT | Summary: The NBN FHA domain binds CK2-phosphorylated SDT repeats of MDC1. Reason: Phosphopeptide recognition by the FHA/BRCT module is the binding mode through which NBN carries out its core chromatin-protein adaptor activity (GO:0140463 in core_functions), so the row is accepted as the specific binding activity that underlies that core function. Supporting Evidence: PMID:18411307 This interaction was constitutive and mediated by binding between the phosphorylated SDT repeats of MDC1 and the phosphate-binding forkhead-associated domain of NBS1. |
| GO:0140031 phosphorylation-dependent protein binding | IDA PMID:18582474 Structure of a second BRCT domain identified in the nijmegen... | ACCEPT | Summary: NBN BRCT2 completes a tandem BRCT with phosphoprotein-binding ability needed for MDC1-dependent relocalization. Reason: Structural and mutational evidence for phosphoprotein binding by NBN. Supporting Evidence: PMID:18582474 most likely through a direct interaction of Nbs1 tandem BRCT domains with phosphorylated MDC1. |
| GO:0140031 phosphorylation-dependent protein binding | IDA PMID:18583988 Phospho-dependent interactions between NBS1 and MDC1 mediate... | ACCEPT | Summary: Direct, phosphorylation-dependent binding of NBN to CK2-phosphorylated MDC1. Reason: Direct evidence of the core activity. Supporting Evidence: PMID:18583988 we establish that this phosphorylation of MDC1 promotes direct, phosphorylation-dependent interactions with NBS1 in a manner that requires the closely apposed FHA and twin BRCT domains in the amino terminus of NBS1. |
| GO:0140031 phosphorylation-dependent protein binding | IDA PMID:18678890 MDC1 regulates intra-S-phase checkpoint by targeting NBS1 to... | ACCEPT | Summary: NBN binds the CK2-site-rich region of MDC1 via FHA and tandem BRCT domains. Reason: Supports phosphorylation-dependent binding by NBN. Supporting Evidence: PMID:18678890 In addition, this interaction requires both the forkhead-associated (FHA) and tandem BRCA1 C-terminal (BRCT) domains of NBS1. |
| GO:0140031 phosphorylation-dependent protein binding | IDA PMID:19804756 A supramodular FHA/BRCT-repeat architecture mediates Nbs1 ad... | ACCEPT | Summary: The coalesced FHA/BRCT-repeat module of Nbs1 binds diphosphorylated motifs in MDC1 and Ctp1/CtIP. Reason: Structural evidence (fission yeast) plus human MDC1 binding data for phosphopeptide recognition by NBN. Supporting Evidence: PMID:19804756 Finally, we establish that human Nbs1 interactions with Mdc1 occur through both its FHA- and BRCT-repeat domains, suggesting how their structural and functional interdependence underpins Nbs1 adaptor functions in the DNA-damage response. |
| GO:0140031 phosphorylation-dependent protein binding | IDA PMID:24534091 Rad17 recruits the MRE11-RAD50-NBS1 complex to regulate the ... | ACCEPT | Summary: NBN binds RAD17 phosphorylated on Thr622 by ATM. Reason: A second phosphorylated recruiter of NBN; supports phosphorylation-dependent binding. Supporting Evidence: PMID:24534091 Rad17 is phosphorylated by ATM at a novel Thr622 site resulting in a direct interaction of Rad17 with NBS1 |
| GO:0140031 phosphorylation-dependent protein binding | IDA PMID:27814491 Nbs1 Converts the Human Mre11/Rad50 Nuclease Complex into an... | ACCEPT | Summary: Phosphorylated CtIP stimulates MRN endonucleolytic cleavage in an NBN-dependent manner. Reason: Supports NBN recognition of phosphorylated CtIP. Supporting Evidence: PMID:27814491 The hMRN endonucleolytic cleavage events are further stimulated by the phosphorylated form of the human C-terminal binding protein-interacting protein (CtIP) DNA repair enzyme |
| GO:0140031 phosphorylation-dependent protein binding | IDA PMID:30787182 NBS1 promotes the endonuclease activity of the MRE11-RAD50 c... | ACCEPT | Summary: NBN FHA and BRCT domains sense CtIP phosphorylation. Reason: Direct reconstitution evidence for phosphorylation-dependent binding by NBN. Supporting Evidence: PMID:30787182 Using a reconstituted system, we show here that NBS1, through its FHA and BRCT domains, functions as a sensor of CtIP phosphorylation. |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:11486038 Mre11 complex and DNA replication: linkage to E2F and sites ... | KEEP AS NON CORE | Summary: The MRE11 complex associates with E2F family members through the NBN N terminus. Reason: The NBN-E2F association near replication origins correlates with S-phase checkpoint proficiency. It is a reported interaction of uncertain functional weight, peripheral to the core repair and signalling functions. Supporting Evidence: PMID:11486038 We show that the Mre11 complex associates with E2F family members via the Nbs1 N terminus. |
| GO:0140463 chromatin-protein adaptor activity | IDA PMID:18411307 Phosphorylation of SDT repeats in the MDC1 N terminus trigge... | ACCEPT | Summary: NBN binds phosphorylated MDC1 on DSB-flanking chromatin and thereby retains MRN there. Reason: GO:0140463 covers an adaptor that keeps a protein, or the complex to which it belongs, at a chromatin region. NBN binds chromatin-bound phospho-MDC1 through its FHA domain and MRE11 through its C terminus, which concentrates MRN at the break. This is the core adaptor function of NBN. Supporting Evidence: PMID:18411307 these data suggest that phosphorylation of the SDT repeats in the MDC1 N terminus functions to recruit NBS1 and, thereby, increases the local concentration of MRN at the sites of chromosomal breakage. |
| GO:0140463 chromatin-protein adaptor activity | IDA PMID:18583988 Phospho-dependent interactions between NBS1 and MDC1 mediate... | ACCEPT | Summary: Phospho-dependent NBN-MDC1 interaction mediates NBN chromatin retention at DSBs. Reason: Same adaptor function. Supporting Evidence: PMID:18583988 we show that these CK2-targeted motifs in MDC1 are required to mediate NBS1 association with chromatin-flanking sites of unrepaired DSBs. |
| GO:0140463 chromatin-protein adaptor activity | IDA PMID:19804756 A supramodular FHA/BRCT-repeat architecture mediates Nbs1 ad... | ACCEPT | Summary: FHA/BRCT supramodule underpins NBN adaptor function. Reason: Same adaptor function. Supporting Evidence: PMID:19804756 suggesting how their structural and functional interdependence underpins Nbs1 adaptor functions in the DNA-damage response. |
| GO:0140463 chromatin-protein adaptor activity | IDA PMID:24534091 Rad17 recruits the MRE11-RAD50-NBS1 complex to regulate the ... | ACCEPT | Summary: Phosphorylated RAD17 binds NBN and recruits MRN and ATM to DSBs. Reason: Same adaptor function, through a second chromatin-associated recruiter. Supporting Evidence: PMID:24534091 resulting in a direct interaction of Rad17 with NBS1, facilitating recruitment of the MRN complex and ATM to the DSB, thereby enhancing ATM signaling. |
| GO:0140463 chromatin-protein adaptor activity | IDA PMID:27814491 Nbs1 Converts the Human Mre11/Rad50 Nuclease Complex into an... | ACCEPT | Summary: NBN converts MRE11-RAD50 into an endo/exonuclease on protein-blocked ends in vitro. Reason: NBN chromatin-protein adaptor activity is well supported for the gene (phospho-MDC1 and phospho-RAD17 tethering of MRN to DSB-flanking chromatin), so the claim is accepted. This purified-protein study shows a distinct NBN activity, stimulation of the MRE11-RAD50 nuclease, which is added as a separate NEW row (nuclease activator activity) rather than substituted for the adaptor term. Only the abstract is cached, so the curator, who read the full text, is deferred to rather than moving this row to the nuclease term. Supporting Evidence: PMID:27814491 These results illuminate the important role of Nbs1 and CtIP in determining the substrates and consequences of human Mre11/Rad50 nuclease activities on protein-DNA lesions. |
| GO:0140463 chromatin-protein adaptor activity | IDA PMID:27889449 Phosphorylated CtIP Functions as a Co-factor of the MRE11-RA... | ACCEPT | Summary: NBN is absolutely required for MRE11 endonuclease activity with phosphorylated CtIP in vitro. Reason: NBN chromatin-protein adaptor activity is well supported for the gene (phospho-MDC1 and phospho-RAD17 tethering of MRN to DSB-flanking chromatin), so the claim is accepted. This purified-protein study shows a distinct NBN activity, stimulation of the MRE11-RAD50 nuclease, which is added as a separate NEW row (nuclease activator activity) rather than substituted for the adaptor term. Only the abstract is cached, so the curator, who read the full text, is deferred to rather than moving this row to the nuclease term. Supporting Evidence: PMID:27889449 Unlike in yeast, where the Xrs2/NBS1 subunit is dispensable in vitro, NBS1 is absolutely required in the human system. |
| GO:0140463 chromatin-protein adaptor activity | IDA PMID:28216226 NBS1 Phosphorylation Status Dictates Repair Choice of Dysfun... | ACCEPT | Summary: NBN annotated as a chromatin-protein adaptor for its YQLSP-mediated docking on the TRF2 TRFH domain at telomeres. Reason: NBN binds telomere-bound TRF2 through its YQLSP motif, and TRF2-dependent docking holds dephosphorylated NBN, and with it MRN, at functional telomeres. Under the GO:0140463 definition (keeping a protein or the complex to which it belongs at a chromatin region) this binding fits NBN, as does its docking on phospho-MDC1 at breaks. The same paper describes the TRF2 TRFH domain as a docking platform that recruits several telomere-associated proteins, so TRF2 is the hub and NBN one of its clients. That bears on which protein a pathway model should place first, not on whether NBN has the activity; the YQLSP-TRFH contact is NBN's own binding surface, and it keeps NBN's complex (MRN) at the telomere, which is what the term describes. Supporting Evidence: PMID:28216226 The crystal structure of the TRF2-NBS1 complex at 3.0 Γ
resolution shows that the NBS1 429YQLSP433 motif interacts specifically with the TRF2TRFH domain. PMID:28216226 Finally, in addition to being a protein docking hub, a recent report suggests that TRF2 could also wrap telomeric DNA around its TRF2TRFH domain PMID:28216226 We have previously shown that the TRFH domains of TRF1 and TRF2 function as a docking platform for various telomeric and telomere-associated proteins PMID:28216226 Thus, the native MRN complex very likely associate with TRF2 with much higher affinity than that of NBS1TBM-TRF2TRFH characterized here |
| GO:0140463 chromatin-protein adaptor activity | IDA PMID:30787182 NBS1 promotes the endonuclease activity of the MRE11-RAD50 c... | ACCEPT | Summary: NBN senses phospho-CtIP and activates MRE11-RAD50 through direct contact with MRE11. Reason: NBN chromatin-protein adaptor activity is well supported for the gene (phospho-MDC1 and phospho-RAD17 tethering of MRN to DSB-flanking chromatin), so the claim is accepted. This purified-protein study shows a distinct NBN activity, stimulation of the MRE11-RAD50 nuclease, which is added as a separate NEW row (nuclease activator activity) rather than substituted for the adaptor term. Only the abstract is cached, so the curator, who read the full text, is deferred to rather than moving this row to the nuclease term. Supporting Evidence: PMID:30787182 NBS1 then activates the MRE11-RAD50 nuclease through direct physical interactions with MRE11. |
| GO:0140463 chromatin-protein adaptor activity | IDA PMID:38961290 NBS1 lactylation is required for efficient DNA repair and ch... | ACCEPT | Summary: NBN K388 lactylation is needed for MRN formation and accumulation of HR proteins at DSBs. Reason: Supports NBN's role in assembling MRN at damaged chromatin, consistent with the adaptor function. Supporting Evidence: PMID:38961290 Lactylation of NBS1 at lysine 388 (K388) is essential for MRE11-RAD50-NBS1 (MRN) complex formation and the accumulation of HR repair proteins at the sites of DNA double-strand breaks. |
| GO:0140463 chromatin-protein adaptor activity | IEA GO_REF:0000107 | ACCEPT | Summary: Electronic transfer from mouse Nbn of chromatin-protein adaptor activity. Reason: Consistent with the human evidence for NBN as the MRN adaptor at damaged chromatin. Supporting Evidence: PMID:18411307 these data suggest that phosphorylation of the SDT repeats in the MDC1 N terminus functions to recruit NBS1 and, thereby, increases the local concentration of MRN at the sites of chromosomal breakage. |
| GO:1904354 negative regulation of telomere capping | IMP PMID:17694070 MRE11-RAD50-NBS1 and ATM function as co-mediators of TRF1 in... | MODIFY | Summary: MRN and ATM control TRF1 association with telomeres; TRF1 telomere binding increases in NBS1-deficient cells. Reason: The paper proposes that MRN-dependent ATM phosphorylation of TRF1 releases TRF1 and promotes telomerase access. This is positive regulation of telomere maintenance, not negative regulation of telomere capping; the abstract says nothing about capping or end protection. Only the abstract was available, so the change is proposed as a refinement in line with the paper's own model rather than as a removal. Proposed replacements: positive regulation of telomere maintenance Supporting Evidence: PMID:17694070 We propose that MRN is required for TRF1 phosphorylation by ATM and that such phosphorylation results in the release of TRF1 from telomeres, promoting telomerase access to the ends of telomeres. |
| GO:1905168 positive regulation of double-strand break repair via homologous recombination | ISS GO_REF:0000024 | MODIFY | Summary: ISS from PELI1 for positive regulation of DSB repair via HR. Reason: The claim that NBN promotes HR is true, but NBN does so as a participant, not as a regulator. It stimulates the MRE11 endonuclease that starts end resection (the NEW nuclease activator activity row) and tethers MRN to DSB chromatin, both steps of HR itself, which this review accepts on GO:0000724. By GO convention a gene product that performs steps of a process is annotated to that process rather than also to its regulation, so the row is modified to GO:0000724 rather than removed. The transfer itself is unsound, as recorded in propagation_review (PELI1 is an E3 ligase whose HR role is to ubiquitinate NBN, so it is not a functional homolog of NBN). Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG ROLE CONFLATION Sources checked: UniProtKB:Q96FA3 Β· PELI1 SUPPORTS SOURCE BUT NOT TARGET PELI1 is a DSB-responsive E3 ubiquitin ligase that promotes HR by K63-ubiquitinating NBN (PMID:30952868). It is not homologous to NBN, and its regulation of HR is an enzyme acting on its substrate, so the transfer to NBN conflates the regulator with the protein it modifies. Proposed replacements: double-strand break repair via homologous recombination Supporting Evidence: PMID:30787182 NBS1 then activates the MRE11-RAD50 nuclease through direct physical interactions with MRE11. PMID:27889449 The human MRE11-RAD50-NBS1 (MRN) and CtIP proteins were implicated in the initiation of DNA end resection PMID:30952868 Here we show that Pellino1 (Peli1) is a DSB-responsive ubiquitin ligase required for the accumulation of DNA damage response proteins and efficient homologous recombination (HR) repair. |
| GO:1990166 protein localization to site of double-strand break | IDA PMID:18411307 Phosphorylation of SDT repeats in the MDC1 N terminus trigge... | ACCEPT | Summary: MDC1 phospho-SDT repeats recruit NBN to DSBs. Reason: NBN brings MRE11-RAD50 to DSBs. Its binding to phospho-MDC1 localizes the MRN complex there. Supporting Evidence: PMID:18411307 these data suggest that phosphorylation of the SDT repeats in the MDC1 N terminus functions to recruit NBS1 and, thereby, increases the local concentration of MRN at the sites of chromosomal breakage. |
| GO:1990166 protein localization to site of double-strand break | IDA PMID:18583988 Phospho-dependent interactions between NBS1 and MDC1 mediate... | ACCEPT | Summary: Phospho-dependent NBN-MDC1 interaction mediates focal assembly of MRN at DSBs. Reason: As above. Supporting Evidence: PMID:18583988 These findings provide a molecular explanation for the MDC1-MRN interaction and yield insights into how MDC1 coordinates the focal assembly and activation of several DDR factors in response to DNA damage. |
| GO:1990166 protein localization to site of double-strand break | IDA PMID:24534091 Rad17 recruits the MRE11-RAD50-NBS1 complex to regulate the ... | ACCEPT | Summary: NBN binding to phospho-RAD17 recruits MRN and ATM to DSBs. Reason: NBN localizes MRN and ATM to the break. Supporting Evidence: PMID:24534091 facilitating recruitment of the MRN complex and ATM to the DSB, thereby enhancing ATM signaling. |
| GO:1990166 protein localization to site of double-strand break | IDA PMID:27814491 Nbs1 Converts the Human Mre11/Rad50 Nuclease Complex into an... | ACCEPT | Summary: In vitro MRN nuclease paper annotated to protein localization to site of DSB. Reason: The abstract shows NBN-dependent processing of adducted DNA ends and stimulation by phosphorylated CtIP, but not localization; the full text was not available to us. The term is well supported for NBN by the MDC1 and RAD17 papers, and NBN recruits phosphorylated CtIP to DSBs (UniProt), so the curator is deferred to. Supporting Evidence: PMID:27814491 The hMRN endonucleolytic cleavage events are further stimulated by the phosphorylated form of the human C-terminal binding protein-interacting protein (CtIP) DNA repair enzyme PMID:18583988 we show that these CK2-targeted motifs in MDC1 are required to mediate NBS1 association with chromatin-flanking sites of unrepaired DSBs. |
| GO:1990166 protein localization to site of double-strand break | IDA PMID:27889449 Phosphorylated CtIP Functions as a Co-factor of the MRE11-RA... | ACCEPT | Summary: In vitro MRN-CtIP endonuclease paper annotated to protein localization to site of DSB. Reason: As for PMID:27814491; the term is correct for NBN and the curator's reading of the full text is deferred to. Supporting Evidence: PMID:27889449 The human MRE11-RAD50-NBS1 (MRN) and CtIP proteins were implicated in the initiation of DNA end resection PMID:24534091 facilitating recruitment of the MRN complex and ATM to the DSB, thereby enhancing ATM signaling. |
| GO:2000781 positive regulation of double-strand break repair | IMP PMID:15790808 ATM activation by DNA double-strand breaks through the Mre11... | KEEP AS NON CORE | Summary: MRN acts as a DSB sensor that recruits and activates ATM. Reason: NBN takes part in DSB repair directly; positive regulation of DSB repair through ATM recruitment and activation is an accurate but secondary framing of the same activity, which is captured more precisely as protein serine/threonine kinase activator activity. Supporting Evidence: PMID:15790808 We show that the Mre11-Rad50-Nbs1 (MRN) complex acts as a double-strand break sensor for ATM and recruits ATM to broken DNA molecules. |
| GO:0170053 nuclease activator activity | IDA PMID:30787182 NBS1 promotes the endonuclease activity of the MRE11-RAD50 c... | NEW | Summary: NBN senses CtIP phosphorylation and directly activates the MRE11-RAD50 nuclease. Reason: Reconstituted human proteins show that NBN binds MRE11 and stimulates its endonuclease, and that NBN is absolutely required for MRN-CtIP endonucleolytic cleavage in the human system. NBN contributes this activity itself, through its FHA/BRCT domains and MRE11-binding C terminus, so it passes the participation test. No current annotation captures it; the closest existing rows were filed under chromatin-protein adaptor activity. The PMID:27814491 quote reports that NBN inhibits MRE11-RAD50 3'-to-5' exonuclease on clean ends while the same study shows NBN-dependent endonucleolytic cleavage of protein-blocked ends; it is cited as evidence that NBN switches the nuclease's specificity, not as evidence against activation. Supporting Evidence: PMID:30787182 NBS1 then activates the MRE11-RAD50 nuclease through direct physical interactions with MRE11. PMID:27889449 Unlike in yeast, where the Xrs2/NBS1 subunit is dispensable in vitro, NBS1 is absolutely required in the human system. PMID:27814491 In contrast, Nbs1 inhibits Mre11/Rad50-catalyzed 3'-to-5' exonucleolytic degradation of clean DNA ends. |
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Download this section (compressed HTML)Q: At functional telomeres, is TRF2 or NBN the better bearer of the adaptor activity that holds MRN at the telomere? The current GO-CAM gomodel:65a1f4f800002884 puts chromatin-protein adaptor activity on NBN with has_input TERF2, while the TRF2-NBS1 structure paper (PMID:28216226) describes the TRF2 TRFH domain as the docking platform for NBN and other telomere-associated proteins.
Q: Does NBN itself contact DNA within the MRN complex, or is damaged DNA binding entirely provided by MRE11 and RAD50? The IBA asserting that NBN enables damaged DNA binding depends on the answer.
Q: Should the PELI1-derived ISS rows (K63-linked ubiquitination and positive regulation of HR) be withdrawn upstream, since NBN is the substrate of PELI1 rather than a homolog with ligase activity?
Experiment: Separation-of-function test of the NBN S432 switch in human cells. Knock in S432A and S432D into the endogenous NBN locus, then deplete TRF2 or POT1-TPP1 and measure classical (LIG4) versus alternative (PARP1/LIG3) telomere fusions, ATM activation and EXO1 recruitment, to test whether the mouse S433 results hold in human cells.
Hypothesis: CDK2 phosphorylation of human NBN S432 is necessary and sufficient to route TRF2-depleted telomeres to classical NHEJ.
Type: genome editing with functional readout
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