XRCC2 (DNA repair protein XRCC2; also FANCU) is one of five human RAD51 paralogs and a RecA/RAD51-family P-loop NTPase. It is an obligate structural subunit of the BCDX2 complex (RAD51B-RAD51C-RAD51D-XRCC2), one of the two classical RAD51-paralog assemblies (the other being CX3, RAD51C-XRCC3). Together with RAD51D, XRCC2 also joins CX3 in a RAD51B-independent X3CDX2 (DX2-CX3) tetramer that stably caps the 5' end of RAD51-ssDNA filaments, with XRCC2 forming the cap, and stimulates RAD51-mediated strand invasion. BCDX2 functions as a homologous-recombination mediator: it binds single-stranded DNA and branched DNA structures (four-way/Holliday junctions and replication forks) and stimulates the nucleation and extension of the RAD51 nucleoprotein filament on RPA-coated ssDNA, an activity essential for homologous recombination. Within the complex, RAD51C-RAD51D-XRCC2 structurally mimic three aligned RAD51 protomers; XRCC2 binds ATP through canonical Walker A/B motifs, but the ATP hydrolysis that drives the high-affinity ssDNA-binding, filament-promoting state is contributed by RAD51B and RAD51C. BCDX2 acts downstream of BRCA2 recruitment and upstream of RAD51 recruitment, and also participates in replication fork remodeling/protection and interstrand crosslink repair. XRCC2 localizes predominantly to the nucleus/nucleoplasm and is also found at centrosomes. Biallelic loss-of-function causes Fanconi anemia complementation group U, and XRCC2 deficiency produces hypersensitivity to DNA cross-linking agents, chromosome instability and defective homologous recombination; hypomorphic variants underlie meiotic phenotypes (spermatogenic failure, premature ovarian failure) and contribute to cancer predisposition.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000400 four-way junction DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: As part of the BCDX2 complex, XRCC2 contributes to specific binding of four-way (Holliday) junction DNA. Experimentally supported and phylogenetically consistent. Reason: The purified BCDX2 complex binds with high specificity to branched DNA including Holliday (four-way) junctions; XRCC2 is an obligate subunit contributing to this DNA-binding activity. The contributes_to qualifier is appropriate for a complex subunit. Supporting Evidence: PMID:20207730 both complexes bind with exceptionally |
| GO:0000724 double-strand break repair via homologous recombination | IBA GO_REF:0000033 | ACCEPT | Summary: Core biological process. XRCC2, via BCDX2, promotes RAD51 filament assembly required for double-strand break repair by homologous recombination. Reason: Well established for XRCC2 and the RAD51 paralogs; XRCC2-deficient cells are defective in HR and RAD51 focus formation. This is the central function of the gene. Supporting Evidence: PMID:37344587 BCDX2 stimulates the nucleation and extension of RAD51 |
| GO:0005657 replication fork | IBA GO_REF:0000033 | ACCEPT | Summary: XRCC2/BCDX2 acts at replication forks, binding fork structures and functioning in fork remodeling, protection and restart. Reason: The BCDX2 complex binds replication-fork DNA with high specificity and restrains fork progression/promotes fork reversal under replication stress. Supporting Evidence: PMID:32669601 the BCDX2 subcomplex restrains fork progression upon stress, promoting fork |
| GO:0005813 centrosome | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: XRCC2 co-localizes with centrosomes; this is a secondary localization associated with a role in mitotic stability rather than the core HR-mediator function. Reason: Centrosome association is experimentally observed but represents a peripheral/secondary activity (mitotic stability) likely downstream of the primary HR role; not a core molecular function of XRCC2. Supporting Evidence: PMID:21276791 XRCC2 and other HR proteins, including the key |
| GO:0033063 Rad51B-Rad51C-Rad51D-XRCC2 complex | IBA GO_REF:0000033 | ACCEPT | Summary: XRCC2 is an obligate subunit of the BCDX2 complex. This is the defining structural annotation for the protein. Reason: Biochemically purified and structurally resolved; XRCC2 is one of the four subunits of BCDX2. Supporting Evidence: PMID:11751635 the five paralogs exist in two distinct complexes in human cells: one contains RAD51B, RAD51C, RAD51D, and XRCC2 (defined as BCDX2) |
| GO:0042148 DNA strand invasion | IBA GO_REF:0000033 | ACCEPT | Summary: XRCC2, via its subcomplex/BCDX2 mediator activity, promotes homologous pairing and strand invasion during HR. Reason: The purified Xrcc2*Rad51D subcomplex catalyzes homologous pairing between ssDNA and dsDNA, and BCDX2 promotes RAD51 filament assembly that carries out strand invasion. Recent reconstitution refines this: stimulation of RAD51-mediated strand invasion is a property of the XRCC3-containing X3CDX2 complex (in which XRCC2 forms the 5' filament cap), whereas the RAD51B (BCDX2) complex showed no such activity. XRCC2's participation in strand invasion is therefore supported, but via X3CDX2 rather than BCDX2. Supporting Evidence: PMID:11834724 pairing between single-stranded and double-stranded DNA PMID:41196948 The XRCC3 complex, and to a lesser extent the CX3 complex, stimulated RAD51-mediated strand invasion, whereas the RAD51B complex showed no activity |
| GO:0000724 double-strand break repair via homologous recombination | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based electronic annotation to the core HR process; consistent with experimental and phylogenetic evidence. Reason: Redundant with, and consistent with, the experimentally and IBA-supported HR annotation. Supporting Evidence: PMID:10517641 XRCC2 is essential for the efficient repair of DNA double-strand breaks by homologous recombination between sister chromatids |
| GO:0003677 DNA binding | IEA GO_REF:0000002 | ACCEPT | Summary: XRCC2, within BCDX2, binds ssDNA and branched DNA. DNA binding is a broad but correct parent term. Reason: Correct though general; more specific supported terms (four-way junction DNA binding) are also annotated. Acceptable as a broad electronic annotation. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: XRCC2 binds ATP via canonical Walker A (K54/T55) and Walker B (D149) motifs, as resolved in the BCDX2 cryo-EM structure. Reason: Directly confirmed structurally; XRCC2 binds ATP even though the catalytic ATPase driving BCDX2's filament-promoting activity is contributed by RAD51B and RAD51C. Supporting Evidence: PMID:37344587 XRCC2 binds ATP in a near-identical arrangement via Walker A K54/T55 and Walker B D149 |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: XRCC2 is a nuclear protein, consistent with its DNA-repair function. Reason: Nuclear localization is experimentally documented (UniProt SUBCELLULAR LOCATION; PMID:21276791). Supporting Evidence: PMID:21276791 XRCC2 and other HR proteins, including the key |
| GO:0005657 replication fork | IEA GO_REF:0000002 | ACCEPT | Summary: Electronic annotation to replication fork, consistent with experimental data. Reason: Redundant with experimentally supported replication-fork annotations. |
| GO:0005813 centrosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Centrosome localization from UniProt subcellular-location mapping; a secondary localization. Reason: Consistent with experimental IDA (PMID:21276791) but peripheral to the core HR-mediator function. |
| GO:0006281 DNA repair | IEA GO_REF:0000002 | ACCEPT | Summary: Broad DNA-repair annotation; correct parent of the specific HR role. Reason: Correct though general; the more specific HR term is also annotated. |
| GO:0033063 Rad51B-Rad51C-Rad51D-XRCC2 complex | IEA GO_REF:0000002 | ACCEPT | Summary: Electronic annotation of BCDX2 membership; consistent with experimental evidence. Reason: Redundant with the experimentally supported BCDX2 complex annotations. |
| GO:0140664 ATP-dependent DNA damage sensor activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro-based electronic mapping propagated from the RecA/RAD51 ATP-binding domain. XRCC2 is a RAD51-filament-assembly mediator, not a demonstrated ATP-dependent DNA damage sensor; the ATP hydrolysis that drives BCDX2 is contributed by RAD51B and RAD51C. Reason: This is an over-propagation of a RecA/RAD51-family ATPase/damage-sensor function onto XRCC2. Structural analysis shows XRCC2 binds but is not established to hydrolyze ATP as a damage sensor; its molecular role is as a mediator subunit promoting RAD51 filament nucleation/extension. The term overstates an independent catalytic sensor activity. Supporting Evidence: PMID:37344587 BCDX2 promotes RAD51 filament nucleation and growth in an ATP hydrolysis dependent manner PMID:11301337 it does not make use of ATP binding to promote this function |
| GO:0005515 protein binding | IPI PMID:10749867 Evidence for simultaneous protein interactions between human... | REMOVE | Summary: Generic protein-binding IPI (RAD51D partner). Uninformative as a molecular function; the biologically meaningful interaction is captured by the BCDX2 complex annotation. Reason: 'protein binding' (GO:0005515) is uninformative per curation guidelines. The underlying RAD51D/paralog interaction is better represented by GO:0033063 (BCDX2 complex). Removing the row does not dispute the reported interaction itself. |
| GO:0005515 protein binding | IPI PMID:10871607 The RAD51 family member, RAD51L3, is a DNA-stimulated ATPase... | REMOVE | Summary: Generic protein-binding IPI (RAD51D/RAD51L3 partner); uninformative as MF. Reason: Uninformative 'protein binding' term; the meaningful RAD51D interaction is captured by the BCDX2 complex annotation. Removing the row does not dispute the reported interaction itself. |
| GO:0005515 protein binding | IPI PMID:11751635 Identification and purification of two distinct complexes co... | REMOVE | Summary: Generic protein-binding IPI within the RAD51-paralog complexes study. Reason: Uninformative 'protein binding'; the same paper supports the specific BCDX2 complex annotation (GO:0033063), which should carry the information. Removing the row does not dispute the reported interaction itself. |
| GO:0005515 protein binding | IPI PMID:11842113 Involvement of Rad51C in two distinct protein complexes of R... | REMOVE | Summary: Generic protein-binding IPI (RAD51C/RAD51D partners in paralog complexes). Reason: Uninformative 'protein binding'; captured better by the BCDX2 complex annotation. Removing the row does not dispute the reported interaction itself. |
| GO:0005515 protein binding | IPI PMID:12975363 Functional interaction between the Bloom's syndrome helicase... | REMOVE | Summary: Generic protein-binding IPI (RAD51D/BLM interaction context). Reason: Uninformative 'protein binding' term for a specific partner interaction. Removing the row does not dispute the reported interaction itself. |
| GO:0005515 protein binding | IPI PMID:16710300 Sws1 is a conserved regulator of homologous recombination in... | REMOVE | Summary: Generic protein-binding IPI (SWS1/HR regulator context). Reason: Uninformative 'protein binding' term. Removing the row does not dispute the reported interaction itself. |
| GO:0005515 protein binding | IPI PMID:24141787 Breast cancer-associated missense mutants of the PALB2 WD40 ... | REMOVE | Summary: Generic protein-binding IPI (PALB2/RAD51C interactome context). Reason: Uninformative 'protein binding' term. Removing the row does not dispute the reported interaction itself. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: High-throughput interactome protein-binding IPI (proteome-scale map). Reason: Uninformative 'protein binding' from a large-scale interactome screen. Removing the row does not dispute the reported interaction itself. |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | REMOVE | Summary: High-throughput interactome protein-binding IPI. Reason: Uninformative 'protein binding' from a large-scale interactome screen. Removing the row does not dispute the reported interaction itself. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: High-throughput interactome protein-binding IPI. Reason: Uninformative 'protein binding' from a large-scale interactome screen. Removing the row does not dispute the reported interaction itself. |
| GO:0005515 protein binding | IPI PMID:28864920 Discovery of mutations in homologous recombination genes in ... | REMOVE | Summary: Protein-binding IPI (HR-gene mutation/interaction study). Reason: Uninformative 'protein binding' term. Removing the row does not dispute the reported interaction itself. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: High-throughput interactome protein-binding IPI (variant interaction landscape). Reason: Uninformative 'protein binding' from a large-scale interactome screen. Removing the row does not dispute the reported interaction itself. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interactome protein-binding IPI. Reason: Uninformative 'protein binding' from a large-scale interactome screen. Removing the row does not dispute the reported interaction itself. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: High-throughput interactome protein-binding IPI (RAD51C/RAD51D partners). Reason: Uninformative 'protein binding' from a large-scale interactome screen. Removing the row does not dispute the reported interaction itself. |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | REMOVE | Summary: Protein-binding IPI (breast-cancer interactome landscape). Reason: Uninformative 'protein binding' from a large-scale interactome screen. Removing the row does not dispute the reported interaction itself. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: High-throughput interactome protein-binding IPI (multimodal cell maps). Reason: Uninformative 'protein binding' from a large-scale interactome screen. Removing the row does not dispute the reported interaction itself. |
| GO:0005657 replication fork | NAS PMID:32669601 Sequential role of RAD51 paralog complexes in replication fo... | ACCEPT | Summary: XRCC2/BCDX2 localizes to and acts at replication forks in fork remodeling and restart. Reason: Single-molecule and cellular data place the BCDX2 subcomplex at stressed replication forks, where it restrains fork progression and promotes fork reversal. Supporting Evidence: PMID:32669601 the BCDX2 subcomplex restrains fork progression upon stress, promoting fork PMID:30566856 restrain active DNA synthesis during |
| GO:0033063 Rad51B-Rad51C-Rad51D-XRCC2 complex | IPI PMID:11751635 Identification and purification of two distinct complexes co... | ACCEPT | Summary: Experimentally purified BCDX2 complex membership. Defining structural annotation for XRCC2. Reason: The four-subunit BCDX2 complex was purified to homogeneity and its composition established biochemically. Supporting Evidence: PMID:11751635 one contains RAD51B, RAD51C, RAD51D, and XRCC2 (defined as BCDX2) |
| GO:0097435 supramolecular fiber organization | IDA PMID:37344587 Structure and function of the RAD51B-RAD51C-RAD51D-XRCC2 tum... | MODIFY | Summary: Captures BCDX2's mediator activity: promoting the nucleation and extension of RAD51 nucleoprotein filaments (supramolecular fibers) on ssDNA. Reason: The 2023 structure/function study directly demonstrates that BCDX2 increases both the quantity (nucleation) and length (extension) of RAD51 filaments in an ATP-hydrolysis-dependent manner. That is XRCC2's core contribution, but supramolecular fiber organization is a generic parent that says nothing about recombinases. GO:0000730 DNA recombinase assembly - "the aggregation, arrangement and bonding together of strand exchange proteins (recombinases) into higher order oligomers on single-stranded DNA" - is literally what this experiment shows, and is the term this same PR uses for RAD51. The generic supramolecular-fiber parent loses the recombinase identity, which is the whole content of the finding. Proposed replacements: DNA recombinase assembly Supporting Evidence: PMID:37344587 we found that BCDX2 increases both the quantity (nucleation) and length (growth) of RAD51 filaments |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685318 | ACCEPT | Summary: Nucleoplasmic localization from Reactome HR pathway (BCDX2 complex formation). Reason: Consistent with the nuclear localization of XRCC2 acting in HR; nucleoplasm is a valid refinement of nucleus. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685341 | ACCEPT | Summary: Nucleoplasmic localization from Reactome (BCDX2 stabilizes RAD51 filament). Reason: Consistent with XRCC2's nuclear HR-mediator function. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685838 | ACCEPT | Summary: Nucleoplasmic localization from Reactome HR pathway. Reason: Consistent with XRCC2's nuclear localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686410 | ACCEPT | Summary: Nucleoplasmic localization from Reactome HR pathway. Reason: Consistent with XRCC2's nuclear localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686440 | ACCEPT | Summary: Nucleoplasmic localization from Reactome HR pathway. Reason: Consistent with XRCC2's nuclear localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686469 | ACCEPT | Summary: Nucleoplasmic localization from Reactome HR pathway. Reason: Consistent with XRCC2's nuclear localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686483 | ACCEPT | Summary: Nucleoplasmic localization from Reactome HR pathway. Reason: Consistent with XRCC2's nuclear localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693539 | ACCEPT | Summary: Nucleoplasmic localization from Reactome HR pathway. Reason: Consistent with XRCC2's nuclear localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693584 | ACCEPT | Summary: Nucleoplasmic localization from Reactome HR pathway. Reason: Consistent with XRCC2's nuclear localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693589 | ACCEPT | Summary: Nucleoplasmic localization from Reactome HR pathway. Reason: Consistent with XRCC2's nuclear localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693593 | ACCEPT | Summary: Nucleoplasmic localization from Reactome HR pathway. Reason: Consistent with XRCC2's nuclear localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693620 | ACCEPT | Summary: Nucleoplasmic localization from Reactome HR pathway. Reason: Consistent with XRCC2's nuclear localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9701199 | ACCEPT | Summary: Nucleoplasmic localization from Reactome HR pathway (defective-BRCA1 context). Reason: Consistent with XRCC2's nuclear localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9704330 | ACCEPT | Summary: Nucleoplasmic localization from Reactome HR pathway (defective-PALB2 context). Reason: Consistent with XRCC2's nuclear localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9704408 | ACCEPT | Summary: Nucleoplasmic localization from Reactome HR pathway (defective-PALB2 context). Reason: Consistent with XRCC2's nuclear localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9709601 | ACCEPT | Summary: Nucleoplasmic localization from Reactome HR pathway (defective-BRCA2 context). Reason: Consistent with XRCC2's nuclear localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9853389 | ACCEPT | Summary: Nucleoplasmic localization from Reactome (FIGNL1 binds RAD51 context). Reason: Consistent with XRCC2's nuclear localization. |
| GO:0000278 mitotic cell cycle | IMP PMID:21276791 Homologous recombination proteins are associated with centro... | KEEP AS NON CORE | Summary: XRCC2-deficient cells show mitotic instability/catastrophe linked to centrosome disruption. A broad, secondary process term. Reason: Experimentally supported but very general and peripheral to the core HR-mediator role; likely an indirect consequence of genome instability rather than a distinct XRCC2 function. Supporting Evidence: PMID:21276791 centrosome disruption is dynamic |
| GO:0000400 four-way junction DNA binding | IDA PMID:20207730 Ring-shaped Rad51 paralog protein complexes bind Holliday ju... | ACCEPT | Summary: Direct EM demonstration that BCDX2 binds Holliday (four-way) junctions with high specificity; XRCC2 contributes to this activity as a complex subunit. Reason: Experimentally supported specific DNA-binding molecular function; contributes_to is the correct qualifier for a subunit of the DNA-binding complex. Supporting Evidence: PMID:20207730 both complexes bind with exceptionally |
| GO:0000724 double-strand break repair via homologous recombination | IMP PMID:23149936 Rad51 paralog complexes BCDX2 and CX3 act at different stage... | ACCEPT | Summary: Loss of BCDX2 function impairs HR; the complex acts downstream of BRCA2 and upstream of RAD51 recruitment. Reason: Directly demonstrated genetic requirement for XRCC2/BCDX2 in the BRCA1-BRCA2-dependent HR pathway. Core function. Supporting Evidence: PMID:23149936 the BCDX2 complex acts downstream of BRCA2 recruitment but |
| GO:0005657 replication fork | IDA PMID:20207730 Ring-shaped Rad51 paralog protein complexes bind Holliday ju... | ACCEPT | Summary: BCDX2 binds replication-fork DNA structures with high specificity (direct EM). Reason: Direct experimental visualization of BCDX2 binding forked DNA; supports replication-fork localization. Supporting Evidence: PMID:20207730 both complexes bind with exceptionally |
| GO:0005813 centrosome | IDA PMID:21276791 Homologous recombination proteins are associated with centro... | KEEP AS NON CORE | Summary: XRCC2 co-localizes with centrosomes throughout the cell cycle (direct observation); a secondary localization. Reason: Experimentally supported but peripheral to the core HR-mediator function; retained as a non-core localization. Supporting Evidence: PMID:21276791 XRCC2 and other HR proteins, including the key |
| GO:0007098 centrosome cycle | IMP PMID:21276791 Homologous recombination proteins are associated with centro... | KEEP AS NON CORE | Summary: XRCC2 deficiency disrupts centrosome integrity, linking XRCC2 to centrosome/mitotic stability. A secondary process. Reason: Experimentally supported but a peripheral role likely secondary to genome-instability effects; not a core molecular function. Supporting Evidence: PMID:21276791 centrosome disruption is dynamic |
| GO:0033063 Rad51B-Rad51C-Rad51D-XRCC2 complex | IDA PMID:11751635 Identification and purification of two distinct complexes co... | ACCEPT | Summary: Direct biochemical demonstration of BCDX2 complex membership. Reason: BCDX2 was purified to homogeneity with XRCC2 as a subunit. Supporting Evidence: PMID:11751635 one contains RAD51B, RAD51C, RAD51D, and XRCC2 (defined as BCDX2) |
| GO:0042148 DNA strand invasion | IDA PMID:11834724 Homologous pairing and ring and filament structure formation... | ACCEPT | Summary: The purified Xrcc2*Rad51D subcomplex catalyzes homologous pairing between ssDNA and dsDNA, the strand-invasion reaction of HR. Reason: Direct in vitro demonstration of homologous-pairing (strand-invasion) activity by an XRCC2-containing subcomplex. Supporting Evidence: PMID:11834724 pairing between single-stranded and double-stranded DNA |
| GO:0006281 DNA repair | IGI PMID:10422536 The XRCC2 and XRCC3 repair genes are required for chromosome... | ACCEPT | Summary: XRCC2 (and XRCC3) are required for chromosome stability; XRCC2-mutant cells accumulate breaks, deletions and translocations. Broad DNA-repair role. Reason: Genetic-interaction evidence that XRCC2 maintains chromosome stability via DNA repair; correct though general parent of the specific HR term. Supporting Evidence: PMID:10422536 play essential roles in |
| GO:0006281 DNA repair | TAS PMID:9628903 The XRCC2 DNA repair gene from human and mouse encodes a nov... | ACCEPT | Summary: XRCC2 identified as a recA/RAD51-family DNA-repair gene that complements cross-linker hypersensitivity of irs1 cells. Reason: Author-stated DNA-repair role, consistent with all downstream evidence. Supporting Evidence: PMID:9628903 elevated in mouse testis, suggesting an additional role |
| GO:0051321 meiotic cell cycle | TAS PMID:9628903 The XRCC2 DNA repair gene from human and mouse encodes a nov... | KEEP AS NON CORE | Summary: XRCC2 has a meiotic role: its transcript is elevated in testis and biallelic hypomorphic variants cause meiotic arrest/infertility (SPGF50, POF17). Reason: Meiotic involvement is genuine (supported by expression and human infertility phenotypes) but represents a tissue/context-specific deployment of the same HR machinery rather than a distinct core molecular function. Supporting Evidence: PMID:9628903 elevated in mouse testis, suggesting an additional role PMID:30042186 XRCC2 recessive mutation causing meiotic arrest and infertility in humans |
| GO:0036297 interstrand cross-link repair | IMP PMID:27208205 Complementation of hypersensitivity to DNA interstrand cross... | NEW | Summary: XRCC2 (FANCU) is required for repair of DNA interstrand crosslinks: wild-type XRCC2 corrects the mitomycin-C hypersensitivity, chromosome breakage and G2-M accumulation of Fanconi anemia patient cells carrying biallelic XRCC2 mutation, placing XRCC2 in the FA-BRCA ICL-repair pathway (acting late, downstream of FANCD2 monoubiquitination). Reason: Not present in GOA but well-evidenced and a genuine gap: XRCC2 is Fanconi anemia complementation group U (FANCU). Interstrand cross-link repair (GO:0036297) is a specific, correctly-branched DNA-repair biological process distinct from the general DNA repair (GO:0006281) and DSBR-HR (GO:0000724) terms already annotated. Genetic complementation of ICL-specific cellular phenotypes directly demonstrates the role. Supporting Evidence: PMID:27208205 all related to the repair of DNA interstrand crosslinks, including |
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Download this section (compressed HTML)Q: Does XRCC2's own ATP binding (Walker A K54/T55, Walker B D149) contribute catalytically to BCDX2 function, or is it purely structural, given that RAD51B and RAD51C provide the coupled ATPase activity that drives RAD51 filament assembly?
Q: Is the centrosome/mitotic-stability phenotype of XRCC2-deficient cells a direct function of XRCC2 at the centrosome, or an indirect consequence of unrepaired DNA damage and genome instability?
Q: How is XRCC2-RAD51D partitioned between BCDX2 (dynamic RAD51 loader) and X3CDX2 (stable 5' filament cap) in cells, and which assembly underlies XRCC2's roles in fork progression, fork protection and ICL repair? Should GO add a complex term for X3CDX2?
Experiment: Separation-of-function XRCC2 Walker-motif mutants (ATP-binding-deficient) reconstituted into BCDX2 to test whether XRCC2 nucleotide binding is required for RAD51 filament nucleation and extension versus complex assembly.
Hypothesis: XRCC2 ATP binding is structural and largely dispensable for the catalytic drive of RAD51 filament assembly, which is provided by RAD51B and RAD51C.
Experiment: Single-molecule assays of RAD51 filament assembly with BCDX2 reconstituted from cancer- and Fanconi-associated XRCC2 variants to map variant effects onto the mediator activity.
Hypothesis: Pathogenic XRCC2 variants impair BCDX2's ability to nucleate and extend RAD51 filaments.
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