RAD51B (RAD51L1, REC2) is one of the five human RAD51 paralogs, RecA/RAD51-family proteins with Walker A/B ATP-binding motifs that work as accessory factors to the RAD51 recombinase. It is found only in the heterotetrameric BCDX2 complex (RAD51B-RAD51C-RAD51D-XRCC2), where it pairs with RAD51C as the BC subcomplex. RAD51B is not part of the RAD51C-XRCC3 (CX3) or XRCC3-RAD51C-RAD51D-XRCC2 (X3CDX2) complexes. Purified RAD51B binds single- and double-stranded DNA, prefers Holliday-junction DNA, and hydrolyses ATP in a DNA-dependent manner. Within BCDX2 it is one of two catalytically active ATPase subunits. The coupled ATPases of RAD51B and RAD51C drive high-affinity binding of BCDX2 to single-stranded DNA, and BCDX2 then stimulates nucleation and extension of RAD51 nucleoprotein filaments on RPA-coated DNA. Its flexible C-terminal domain is thought to engage RAD51 during filament nucleation. BCDX2 acts in the BRCA1-BRCA2-dependent homologous recombination pathway, downstream of BRCA2 recruitment and upstream of RAD51 loading. It also binds replication-fork and Holliday-junction DNA and, together with RAD51, protects stalled and reversed replication forks from nucleolytic degradation. Rad51b loss is embryonic lethal in mice. In human cell lines RAD51B-deficient cells have the mildest homologous recombination defects of the five paralogs. RAD51B is a breast cancer susceptibility locus and a recurrent translocation partner of HMGA2 in uterine leiomyoma.
Definition: Binding to a DNA strand exchange protein (recombinase) and to single-stranded DNA so as to promote nucleation and extension of the recombinase nucleoprotein filament, including displacement of the single-stranded DNA-binding protein that otherwise occludes the substrate. The loader is not itself a strand exchange protein and does not catalyse strand exchange.
Justification: Same proposal as in the RAD51C review. GO has the process GO:0000730 DNA recombinase assembly but no molecular function for the mediator activity that carries it out. As a result, the RAD51 paralogs carry borrowed terms such as GO:0140664 ATP-dependent DNA damage sensor activity, which describes a sensor rather than a loader. BCDX2, in which RAD51B provides one of the two coupled ATPase sites, is a defining example.
Parent term: single-stranded DNA binding
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000400 four-way junction DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: Contributes to four-way junction DNA binding as part of BCDX2 (IBA). Reason: Purified BCDX2 binds Holliday junctions and forks with high specificity (PMID:20207730), and isolated RAD51B also prefers Holliday-junction DNA (PMID:12441335). contributes_to is appropriate for the complex-level activity. Supporting Evidence: PMID:12441335 the Rad51B protein only bound to the synthetic Holliday junction PMID:20207730 both complexes bind with exceptionally high specificity to the DNA junctions |
| GO:0000400 four-way junction DNA binding | IDA PMID:20207730 Ring-shaped Rad51 paralog protein complexes bind Holliday ju... | ACCEPT | Summary: Contributes to four-way junction DNA binding as part of BCDX2 (IDA). Reason: Purified BCDX2 binds Holliday junctions and forks with high specificity (PMID:20207730), and isolated RAD51B also prefers Holliday-junction DNA (PMID:12441335). contributes_to is appropriate for the complex-level activity. Supporting Evidence: PMID:12441335 the Rad51B protein only bound to the synthetic Holliday junction PMID:20207730 both complexes bind with exceptionally high specificity to the DNA junctions |
| GO:0000724 double-strand break repair via homologous recombination | IBA GO_REF:0000033 | ACCEPT | Summary: RAD51B functions in DSB repair via homologous recombination (IBA). Reason: This is the central biological role. BCDX2 is required for RAD51 loading and acts between BRCA2 recruitment and RAD51 recruitment. Through its coupled ATPase with RAD51C, RAD51B directly contributes to the mediator step. Supporting Evidence: PMID:23149936 the BCDX2 complex acts downstream of BRCA2 recruitment but upstream of Rad51 recruitment PMID:37344587 BCDX2 stimulates the nucleation and extension of RAD51 |
| GO:0000724 double-strand break repair via homologous recombination | IEA GO_REF:0000002 | ACCEPT | Summary: RAD51B functions in DSB repair via homologous recombination (IEA). Reason: This is the central biological role. BCDX2 is required for RAD51 loading and acts between BRCA2 recruitment and RAD51 recruitment. Through its coupled ATPase with RAD51C, RAD51B directly contributes to the mediator step. Supporting Evidence: PMID:23149936 the BCDX2 complex acts downstream of BRCA2 recruitment but upstream of Rad51 recruitment PMID:37344587 BCDX2 stimulates the nucleation and extension of RAD51 |
| GO:0000724 double-strand break repair via homologous recombination | IMP PMID:23149936 Rad51 paralog complexes BCDX2 and CX3 act at different stage... | ACCEPT | Summary: RAD51B functions in DSB repair via homologous recombination (IMP). Reason: This is the central biological role. BCDX2 is required for RAD51 loading and acts between BRCA2 recruitment and RAD51 recruitment. Through its coupled ATPase with RAD51C, RAD51B directly contributes to the mediator step. Supporting Evidence: PMID:23149936 the BCDX2 complex acts downstream of BRCA2 recruitment but upstream of Rad51 recruitment PMID:37344587 BCDX2 stimulates the nucleation and extension of RAD51 |
| GO:0003677 DNA binding | IEA GO_REF:0000002 | ACCEPT | Summary: DNA binding (IEA). Reason: Accurate general term. The more informative ssDNA, dsDNA and four-way-junction binding terms are annotated separately. Supporting Evidence: PMID:12441335 the purified Rad51B protein bound to single-stranded DNA and double-stranded DNA in the presence of ATP |
| GO:0003677 DNA binding | TAS PMID:9512535 Isolation of novel human and mouse genes of the recA/RAD51 r... | ACCEPT | Summary: DNA binding (TAS). Reason: Accurate general term. The more informative ssDNA, dsDNA and four-way-junction binding terms are annotated separately. Supporting Evidence: PMID:12441335 the purified Rad51B protein bound to single-stranded DNA and double-stranded DNA in the presence of ATP |
| GO:0003690 double-stranded DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: Double-stranded DNA binding (IBA). Reason: Purified RAD51B binds dsDNA in the presence of ATP (PMID:12441335). This is accurate, although ssDNA and branched-DNA binding are more functionally relevant. Supporting Evidence: PMID:12441335 the purified Rad51B protein bound to single-stranded DNA and double-stranded DNA in the presence of ATP |
| GO:0003690 double-stranded DNA binding | IDA PMID:12441335 Holliday junction binding activity of the human Rad51B prote... | ACCEPT | Summary: Double-stranded DNA binding (IDA). Reason: Purified RAD51B binds dsDNA in the presence of ATP (PMID:12441335). This is accurate, although ssDNA and branched-DNA binding are more functionally relevant. Supporting Evidence: PMID:12441335 the purified Rad51B protein bound to single-stranded DNA and double-stranded DNA in the presence of ATP |
| GO:0003697 single-stranded DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: Single-stranded DNA binding (IBA). Reason: Shown directly for RAD51B and for the RAD51B-RAD51C heterodimer. High-affinity ssDNA binding of BCDX2 depends on the RAD51B-RAD51C ATPase cycle and underlies the mediator function. Supporting Evidence: PMID:12441335 the purified Rad51B protein bound to single-stranded DNA and double-stranded DNA in the presence of ATP PMID:11751636 Rad51B-Rad51C complex has ssDNA binding and ssDNA-stimulated ATPase activities |
| GO:0003697 single-stranded DNA binding | IDA PMID:12441335 Holliday junction binding activity of the human Rad51B prote... | ACCEPT | Summary: Single-stranded DNA binding (IDA). Reason: Shown directly for RAD51B and for the RAD51B-RAD51C heterodimer. High-affinity ssDNA binding of BCDX2 depends on the RAD51B-RAD51C ATPase cycle and underlies the mediator function. Supporting Evidence: PMID:12441335 the purified Rad51B protein bound to single-stranded DNA and double-stranded DNA in the presence of ATP PMID:11751636 Rad51B-Rad51C complex has ssDNA binding and ssDNA-stimulated ATPase activities |
| GO:0005515 protein binding | IPI PMID:11751635 Identification and purification of two distinct complexes co... | REMOVE | Summary: IPI protein binding between RAD51B and RAD51C (PMID:11751635), from a targeted interaction study. Reason: GO:0005515 protein binding is uninformative as a molecular function. This interaction with another RAD51 paralog reflects RAD51B's membership of the BCDX2 complex, which is already captured by GO:0033063 Rad51B-Rad51C-Rad51D-XRCC2 complex and by the core functions. Removing the row does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:11751635 Identification and purification of two distinct complexes co... | REMOVE | Summary: IPI protein binding between RAD51B and RAD51D (PMID:11751635), from a targeted interaction study. Reason: GO:0005515 protein binding is uninformative as a molecular function. This interaction with another RAD51 paralog reflects RAD51B's membership of the BCDX2 complex, which is already captured by GO:0033063 Rad51B-Rad51C-Rad51D-XRCC2 complex and by the core functions. Removing the row does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:11842113 Involvement of Rad51C in two distinct protein complexes of R... | REMOVE | Summary: IPI protein binding between RAD51B and RAD51C (PMID:11842113), from a targeted interaction study. Reason: GO:0005515 protein binding is uninformative as a molecular function. This interaction with another RAD51 paralog reflects RAD51B's membership of the BCDX2 complex, which is already captured by GO:0033063 Rad51B-Rad51C-Rad51D-XRCC2 complex and by the core functions. Removing the row does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:11842113 Involvement of Rad51C in two distinct protein complexes of R... | REMOVE | Summary: IPI protein binding between RAD51B and RAD51D (PMID:11842113), from a targeted interaction study. Reason: GO:0005515 protein binding is uninformative as a molecular function. This interaction with another RAD51 paralog reflects RAD51B's membership of the BCDX2 complex, which is already captured by GO:0033063 Rad51B-Rad51C-Rad51D-XRCC2 complex and by the core functions. Removing the row does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:21965664 hSWS1·SWSAP1 is an evolutionarily conserved complex required... | REMOVE | Summary: IPI protein binding between RAD51B and SWSAP1 (PMID:21965664), from a targeted interaction study. Reason: GO:0005515 protein binding is uninformative. The interaction links the RAD51 paralogs to the SWS1-SWSAP1 (Shu) complex in HR, but no more informative molecular function can be inferred from binding data alone. |
| GO:0005515 protein binding | IPI PMID:24141787 Breast cancer-associated missense mutants of the PALB2 WD40 ... | REMOVE | Summary: IPI protein binding between RAD51B and RAD51C (PMID:24141787), from a targeted interaction study. Reason: GO:0005515 protein binding is uninformative as a molecular function. This interaction with another RAD51 paralog reflects RAD51B's membership of the BCDX2 complex, which is already captured by GO:0033063 Rad51B-Rad51C-Rad51D-XRCC2 complex and by the core functions. Removing the row does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: IPI protein binding between RAD51B and FAM9B (PMID:25416956), from a high-throughput interactome screen. Reason: GO:0005515 protein binding is uninformative as a molecular function. The partner has no established role in recombination, and no specific function can be inferred from a binary interaction alone. Removing the row does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:28864920 Discovery of mutations in homologous recombination genes in ... | REMOVE | Summary: IPI protein binding between RAD51B and RAD51C (PMID:28864920), from a targeted interaction study. Reason: GO:0005515 protein binding is uninformative as a molecular function. This interaction with another RAD51 paralog reflects RAD51B's membership of the BCDX2 complex, which is already captured by GO:0033063 Rad51B-Rad51C-Rad51D-XRCC2 complex and by the core functions. Removing the row does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: IPI protein binding between RAD51B and MEOX2 (PMID:32296183), from a high-throughput interactome screen. Reason: GO:0005515 protein binding is uninformative as a molecular function. The partner has no established role in recombination, and no specific function can be inferred from a binary interaction alone. Removing the row does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: IPI protein binding between RAD51B and RPAIN (PMID:32296183), from a high-throughput interactome screen. Reason: GO:0005515 protein binding is uninformative as a molecular function. The partner has no established role in recombination, and no specific function can be inferred from a binary interaction alone. Removing the row does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: IPI protein binding between RAD51B and RAD51C (PMID:33961781), from a high-throughput interactome screen. Reason: GO:0005515 protein binding is uninformative as a molecular function. This interaction with another RAD51 paralog reflects RAD51B's membership of the BCDX2 complex, which is already captured by GO:0033063 Rad51B-Rad51C-Rad51D-XRCC2 complex and by the core functions. Removing the row does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: IPI protein binding between RAD51B and RAD51D (PMID:33961781), from a high-throughput interactome screen. Reason: GO:0005515 protein binding is uninformative as a molecular function. This interaction with another RAD51 paralog reflects RAD51B's membership of the BCDX2 complex, which is already captured by GO:0033063 Rad51B-Rad51C-Rad51D-XRCC2 complex and by the core functions. Removing the row does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | REMOVE | Summary: IPI protein binding between RAD51B and RAD51C (PMID:34591612), from a high-throughput interactome screen. Reason: GO:0005515 protein binding is uninformative as a molecular function. This interaction with another RAD51 paralog reflects RAD51B's membership of the BCDX2 complex, which is already captured by GO:0033063 Rad51B-Rad51C-Rad51D-XRCC2 complex and by the core functions. Removing the row does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | REMOVE | Summary: IPI protein binding between RAD51B and RAD51D (PMID:34591612), from a high-throughput interactome screen. Reason: GO:0005515 protein binding is uninformative as a molecular function. This interaction with another RAD51 paralog reflects RAD51B's membership of the BCDX2 complex, which is already captured by GO:0033063 Rad51B-Rad51C-Rad51D-XRCC2 complex and by the core functions. Removing the row does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: IPI protein binding between RAD51B and RAD51C (PMID:40205054), from a high-throughput interactome screen. Reason: GO:0005515 protein binding is uninformative as a molecular function. This interaction with another RAD51 paralog reflects RAD51B's membership of the BCDX2 complex, which is already captured by GO:0033063 Rad51B-Rad51C-Rad51D-XRCC2 complex and by the core functions. Removing the row does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: IPI protein binding between RAD51B and RAD51D (PMID:40205054), from a high-throughput interactome screen. Reason: GO:0005515 protein binding is uninformative as a molecular function. This interaction with another RAD51 paralog reflects RAD51B's membership of the BCDX2 complex, which is already captured by GO:0033063 Rad51B-Rad51C-Rad51D-XRCC2 complex and by the core functions. Removing the row does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:9469824 Isolation and characterization of RAD51C, a new human member... | REMOVE | Summary: IPI protein binding between RAD51B and RAD51C (PMID:9469824), from a targeted interaction study. Reason: GO:0005515 protein binding is uninformative as a molecular function. This interaction with another RAD51 paralog reflects RAD51B's membership of the BCDX2 complex, which is already captured by GO:0033063 Rad51B-Rad51C-Rad51D-XRCC2 complex and by the core functions. Removing the row does not mean the interaction is false. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding (IEA, InterPro). Reason: RAD51B has functional Walker A/B motifs and hydrolyses ATP. ATP binding by the RAD51B site is part of the coupled ATPase that drives BCDX2 activity. Supporting Evidence: PMID:12441335 hydrolyzed ATP in a DNA-dependent manner PMID:37344587 in reactions that depend on the coupled ATPase activities of RAD51B and RAD51C |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Nuclear localization (IEA). Reason: Consistent with RAD51B's nuclear role in homologous recombination. |
| GO:0005634 nucleus | TAS PMID:9512535 Isolation of novel human and mouse genes of the recA/RAD51 r... | ACCEPT | Summary: Nuclear localization (TAS). Reason: Consistent with RAD51B's nuclear role in homologous recombination. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685318 | ACCEPT | Summary: Nucleoplasm (TAS, Reactome:R-HSA-5685318). Reason: Consistent with RAD51B's nuclear role in homologous recombination. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685341 | ACCEPT | Summary: Nucleoplasm (TAS, Reactome:R-HSA-5685341). Reason: Consistent with RAD51B's nuclear role in homologous recombination. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685838 | ACCEPT | Summary: Nucleoplasm (TAS, Reactome:R-HSA-5685838). Reason: Consistent with RAD51B's nuclear role in homologous recombination. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686410 | ACCEPT | Summary: Nucleoplasm (TAS, Reactome:R-HSA-5686410). Reason: Consistent with RAD51B's nuclear role in homologous recombination. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686440 | ACCEPT | Summary: Nucleoplasm (TAS, Reactome:R-HSA-5686440). Reason: Consistent with RAD51B's nuclear role in homologous recombination. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686469 | ACCEPT | Summary: Nucleoplasm (TAS, Reactome:R-HSA-5686469). Reason: Consistent with RAD51B's nuclear role in homologous recombination. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686483 | ACCEPT | Summary: Nucleoplasm (TAS, Reactome:R-HSA-5686483). Reason: Consistent with RAD51B's nuclear role in homologous recombination. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693539 | ACCEPT | Summary: Nucleoplasm (TAS, Reactome:R-HSA-5693539). Reason: Consistent with RAD51B's nuclear role in homologous recombination. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693584 | ACCEPT | Summary: Nucleoplasm (TAS, Reactome:R-HSA-5693584). Reason: Consistent with RAD51B's nuclear role in homologous recombination. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693589 | ACCEPT | Summary: Nucleoplasm (TAS, Reactome:R-HSA-5693589). Reason: Consistent with RAD51B's nuclear role in homologous recombination. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693593 | ACCEPT | Summary: Nucleoplasm (TAS, Reactome:R-HSA-5693593). Reason: Consistent with RAD51B's nuclear role in homologous recombination. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693620 | ACCEPT | Summary: Nucleoplasm (TAS, Reactome:R-HSA-5693620). Reason: Consistent with RAD51B's nuclear role in homologous recombination. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9701199 | ACCEPT | Summary: Nucleoplasm (TAS, Reactome:R-HSA-9701199). Reason: Consistent with RAD51B's nuclear role in homologous recombination. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9704330 | ACCEPT | Summary: Nucleoplasm (TAS, Reactome:R-HSA-9704330). Reason: Consistent with RAD51B's nuclear role in homologous recombination. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9704408 | ACCEPT | Summary: Nucleoplasm (TAS, Reactome:R-HSA-9704408). Reason: Consistent with RAD51B's nuclear role in homologous recombination. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9709601 | ACCEPT | Summary: Nucleoplasm (TAS, Reactome:R-HSA-9709601). Reason: Consistent with RAD51B's nuclear role in homologous recombination. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-983218 | ACCEPT | Summary: Nucleoplasm (TAS, Reactome:R-HSA-983218). Reason: Consistent with RAD51B's nuclear role in homologous recombination. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-983285 | ACCEPT | Summary: Nucleoplasm (TAS, Reactome:R-HSA-983285). Reason: Consistent with RAD51B's nuclear role in homologous recombination. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9853389 | ACCEPT | Summary: Nucleoplasm (TAS, Reactome:R-HSA-9853389). Reason: Consistent with RAD51B's nuclear role in homologous recombination. |
| GO:0005657 replication fork | IBA GO_REF:0000033 | ACCEPT | Summary: Located at replication forks (IBA). Reason: BCDX2 binds fork DNA with high specificity and acts at stressed forks, where it restrains fork progression and protects reversed forks. Supporting Evidence: PMID:20207730 both complexes bind with exceptionally high specificity to the DNA junctions PMID:32669601 the BCDX2 subcomplex restrains fork progression upon stress, promoting fork reversal |
| GO:0005657 replication fork | IDA PMID:20207730 Ring-shaped Rad51 paralog protein complexes bind Holliday ju... | ACCEPT | Summary: Located at replication forks (IDA). Reason: BCDX2 binds fork DNA with high specificity and acts at stressed forks, where it restrains fork progression and protects reversed forks. Supporting Evidence: PMID:20207730 both complexes bind with exceptionally high specificity to the DNA junctions PMID:32669601 the BCDX2 subcomplex restrains fork progression upon stress, promoting fork reversal |
| GO:0005657 replication fork | NAS PMID:32669601 Sequential role of RAD51 paralog complexes in replication fo... | ACCEPT | Summary: Located at replication forks (NAS). Reason: BCDX2 binds fork DNA with high specificity and acts at stressed forks, where it restrains fork progression and protects reversed forks. Supporting Evidence: PMID:20207730 both complexes bind with exceptionally high specificity to the DNA junctions PMID:32669601 the BCDX2 subcomplex restrains fork progression upon stress, promoting fork reversal |
| GO:0005694 chromosome | IEA GO_REF:0000117 | ACCEPT | Summary: Chromosome (IEA, ARBA). Reason: Consistent with RAD51B acting on chromatin at DNA breaks and replication forks. |
| GO:0006281 DNA repair | IEA GO_REF:0000002 | ACCEPT | Summary: DNA repair (IEA). Reason: Correct general parent of the specific homologous recombination term. |
| GO:0006281 DNA repair | TAS PMID:9512535 Isolation of novel human and mouse genes of the recA/RAD51 r... | ACCEPT | Summary: DNA repair (TAS). Reason: Correct general parent of the specific homologous recombination term. |
| GO:0006302 double-strand break repair | IEA GO_REF:0000117 | ACCEPT | Summary: Double-strand break repair (IEA, ARBA). Reason: Correct parent of GO:0000724. |
| GO:0006310 DNA recombination | TAS PMID:9512535 Isolation of novel human and mouse genes of the recA/RAD51 r... | ACCEPT | Summary: DNA recombination (TAS). Reason: Correct general term for a RAD51 paralog that functions in homologous recombination. |
| GO:0007131 reciprocal meiotic recombination | TAS PMID:9441753 Identification of a novel human RAD51 homolog, RAD51B. | MARK AS OVER ANNOTATED | Summary: Reciprocal meiotic recombination (TAS, gene discovery paper). Reason: The source only speculates about a meiotic role on the basis of RAD51 homology and expression. RAD51B has no IBA for meiotic recombination, and Rad51b knockout mice die early in embryogenesis, so there are no meiotic data. A meiotic function is plausible but unsupported for human RAD51B. Supporting Evidence: PMID:9441753 suggest a role for RAD51B in meiotic recombination and/or recombinational repair PMID:10567591 no homozygous pups were born after interbreeding of heterozygous mice |
| GO:0008094 ATP-dependent activity, acting on DNA | IBA GO_REF:0000033 | ACCEPT | Summary: ATP-dependent activity, acting on DNA (IBA); RAD51B is a DNA-stimulated ATPase. Reason: Isolated RAD51B hydrolyses ATP in a DNA-dependent manner, and in BCDX2 RAD51B is one of two catalytically active ATPase subunits (with RAD51C). It has the catalytic glutamate (E144) that RAD51D and XRCC2 lack. The IBA is therefore well grounded for RAD51B. The RAD51C ATPase is the more critical of the two, since BCDX2 with an inactive RAD51B site keeps partial activity. Supporting Evidence: PMID:12441335 hydrolyzed ATP in a DNA-dependent manner PMID:37344587 in reactions that depend on the coupled ATPase activities of RAD51B and RAD51C PMID:37344587 ATPase deficient BCE161ADX2 and BE144ACE161ADX2 complexes failed to promote RAD51AF488 assembly, whereas BE144ACDX2 retained partial stimulation relative to wild-type |
| GO:0008094 ATP-dependent activity, acting on DNA | IDA PMID:12441335 Holliday junction binding activity of the human Rad51B prote... | ACCEPT | Summary: ATP-dependent activity, acting on DNA (IDA); RAD51B is a DNA-stimulated ATPase. Reason: Isolated RAD51B hydrolyses ATP in a DNA-dependent manner, and in BCDX2 RAD51B is one of two catalytically active ATPase subunits (with RAD51C). It has the catalytic glutamate (E144) that RAD51D and XRCC2 lack. The IBA is therefore well grounded for RAD51B. The RAD51C ATPase is the more critical of the two, since BCDX2 with an inactive RAD51B site keeps partial activity. Supporting Evidence: PMID:12441335 hydrolyzed ATP in a DNA-dependent manner PMID:37344587 in reactions that depend on the coupled ATPase activities of RAD51B and RAD51C PMID:37344587 ATPase deficient BCE161ADX2 and BE144ACE161ADX2 complexes failed to promote RAD51AF488 assembly, whereas BE144ACDX2 retained partial stimulation relative to wild-type |
| GO:0010971 positive regulation of G2/M transition of mitotic cell cycle | IMP PMID:23108668 The RAD51 paralogs ensure cellular protection against mitoti... | KEEP AS NON CORE | Summary: Positive regulation of G2/M transition (IMP): RAD51B knockdown causes G2/M arrest in HeLa cells. Reason: The phenotype is experimentally supported, but G2/M arrest after depletion of an HR factor is most likely an indirect checkpoint response to unrepaired damage, not a regulatory activity of RAD51B. Kept as non-core, consistent with the identical RAD51C row. Supporting Evidence: PMID:23108668 inhibition of RAD51B or RAD51C induces G2/M cell cycle arrest in HeLa cells |
| GO:0033063 Rad51B-Rad51C-Rad51D-XRCC2 complex | IBA GO_REF:0000033 | ACCEPT | Summary: RAD51B is a subunit of the BCDX2 complex (IBA). Reason: Core and well-established membership, shown by co-purification of the four-subunit complex and by cryo-EM structures. RAD51B is the subunit specific to BCDX2. Supporting Evidence: PMID:11751635 one contains RAD51B, RAD51C, RAD51D, and XRCC2 (defined as BCDX2) PMID:37344587 RAD51C-RAD51D-XRCC2 mimics three RAD51 protomers aligned within a nucleoprotein filament, whereas RAD51B is highly dynamic |
| GO:0033063 Rad51B-Rad51C-Rad51D-XRCC2 complex | IDA PMID:11751635 Identification and purification of two distinct complexes co... | ACCEPT | Summary: RAD51B is a subunit of the BCDX2 complex (IDA). Reason: Core and well-established membership, shown by co-purification of the four-subunit complex and by cryo-EM structures. RAD51B is the subunit specific to BCDX2. Supporting Evidence: PMID:11751635 one contains RAD51B, RAD51C, RAD51D, and XRCC2 (defined as BCDX2) PMID:37344587 RAD51C-RAD51D-XRCC2 mimics three RAD51 protomers aligned within a nucleoprotein filament, whereas RAD51B is highly dynamic |
| GO:0033063 Rad51B-Rad51C-Rad51D-XRCC2 complex | IEA GO_REF:0000002 | ACCEPT | Summary: RAD51B is a subunit of the BCDX2 complex (IEA). Reason: Core and well-established membership, shown by co-purification of the four-subunit complex and by cryo-EM structures. RAD51B is the subunit specific to BCDX2. Supporting Evidence: PMID:11751635 one contains RAD51B, RAD51C, RAD51D, and XRCC2 (defined as BCDX2) PMID:37344587 RAD51C-RAD51D-XRCC2 mimics three RAD51 protomers aligned within a nucleoprotein filament, whereas RAD51B is highly dynamic |
| GO:0033063 Rad51B-Rad51C-Rad51D-XRCC2 complex | IPI PMID:11751635 Identification and purification of two distinct complexes co... | ACCEPT | Summary: RAD51B is a subunit of the BCDX2 complex (IPI). Reason: Core and well-established membership, shown by co-purification of the four-subunit complex and by cryo-EM structures. RAD51B is the subunit specific to BCDX2. Supporting Evidence: PMID:11751635 one contains RAD51B, RAD51C, RAD51D, and XRCC2 (defined as BCDX2) PMID:37344587 RAD51C-RAD51D-XRCC2 mimics three RAD51 protomers aligned within a nucleoprotein filament, whereas RAD51B is highly dynamic |
| GO:0097435 supramolecular fiber organization | IDA PMID:37344587 Structure and function of the RAD51B-RAD51C-RAD51D-XRCC2 tum... | MODIFY | Summary: Supramolecular fiber organization (IDA): BCDX2 promotes RAD51 filament nucleation and extension. Reason: The experiment shows that BCDX2 increases the number and length of RAD51 nucleoprotein filaments in a way that depends on ATP hydrolysis by RAD51B and RAD51C. GO:0000730 DNA recombinase assembly ('the aggregation, arrangement and bonding together of strand exchange proteins (recombinases) into higher order oligomers on single-stranded DNA') describes this precisely. The same replacement is made in the RAD51C and XRCC2 reviews. Proposed replacements: DNA recombinase assembly Supporting Evidence: PMID:37344587 we found that BCDX2 increases both the quantity (nucleation) and length (growth) of RAD51 filaments PMID:37344587 Together, these results show that BCDX2 promotes RAD51 filament nucleation and growth in an ATP hydrolysis dependent manner |
| GO:0140664 ATP-dependent DNA damage sensor activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: ATP-dependent DNA damage sensor activity (IEA, InterPro RecA/RAD51 domain mapping). Reason: This term describes a molecule that recognises damaged DNA and initiates a signalling response. RAD51B's ATPase drives high-affinity ssDNA binding of BCDX2 and RAD51 filament assembly (a mediator or loader role), not damage signalling. The sibling RAD51C and XRCC2 reviews make the same call for the same InterPro-derived row. The mediator activity has no GO molecular function and is filed as a proposed new term. Supporting Evidence: PMID:37344587 BCDX2 stimulates the nucleation and extension of RAD51 |
| GO:0031297 replication fork processing | IDA PMID:37843130 RAD51 paralogs synergize with RAD51 to protect reversed fork... | NEW | Summary: BCDX2 (including RAD51B) works with RAD51 filaments to protect stalled or reversed fork DNA from MRE11 and EXO1. Reason: Fork protection is a distinct, well-supported role of BCDX2 beyond DSB repair. Purified BCDX2 has no fork-reversal activity of its own, but it acts directly with RAD51 to protect the regressed arm. The trigger review assigns the BC subcomplex specifically to protecting FANCM-remodelled forks. RAD51B therefore does some of the work (stabilising the protective RAD51 filament) and is not just required for it. Comparator: RAD51C carries GO:0031297. The more specific GO:0071932 replication fork reversal is not proposed, because BCDX2 lacks reversal activity in vitro. Supporting Evidence: PMID:37843130 BCDX2 significantly synergizes with RAD51 to protect DNA against attack by the nucleases MRE11 and EXO1 PMID:37843130 both RAD51 paralog complexes lack fork reversal activities PMID:42682019 The DX2 and CX3 complexes stabilize forks that have been remodeled by FBH1, while the BC subcomplex protects forks remodeled by the FANCM translocase |
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Download this section (compressed HTML)Q: Why are RAD51B-deficient human cells much less affected than cells lacking RAD51C, RAD51D or XRCC2, when RAD51B is essential in mice? Can RAD51B-independent X3CDX2 or CX3 complexes partly substitute for BCDX2 in RAD51 filament assembly?
Q: Does the flexible RAD51B C-terminal domain contact RAD51 directly during filament nucleation, and how does RAD51B ATP hydrolysis change that contact?
Q: Is the reported specificity of the BC subcomplex for FANCM-remodelled forks, as opposed to DX2/CX3 at FBH1-remodelled forks, a property of BC acting outside BCDX2, or of the intact tetramer?
Experiment: Reconstitute BCDX2 with RAD51B catalytic (E144A) or C-terminal-domain deletion mutants and measure RAD51 filament nucleation and protection of reversed forks against MRE11 in single-molecule assays.
Hypothesis: The RAD51B C-terminal domain and its ATPase site are needed for efficient RAD51 nucleation, and RAD51C provides the dominant catalytic contribution.
Type: biochemical reconstitution
Experiment: Combine RAD51B knockout with XRCC3 or FANCM depletion in human cells and measure HR (DR-GFP), RAD51 foci and nascent-strand degradation.
Hypothesis: Mild RAD51B-null phenotypes reflect compensation by RAD51B-independent paralog complexes; the double defects will be synergistic.
Type: genetic interaction
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