RAD51D

UniProt ID: O75771
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

RAD51D (RAD51L3, TRAD) is one of the five human RAD51 paralogs, RecA/RAD51-family proteins that act as accessory factors to the RAD51 recombinase in homologous recombination. RAD51D binds XRCC2 directly to form the DX2 subcomplex. DX2 is part of the heterotetrameric BCDX2 complex (RAD51B-RAD51C-RAD51D-XRCC2) and can also join RAD51C-XRCC3 to form the X3CDX2 complex. In BCDX2, RAD51C-RAD51D-XRCC2 forms a RAD51-filament-like arrangement, and the complex stimulates nucleation and extension of RAD51 filaments on RPA-coated single-stranded DNA, downstream of BRCA2 and upstream of RAD51 loading. X3CDX2 caps the 5' ends of RAD51 filaments and promotes homologous pairing. RAD51D binds ssDNA through its N-terminal domain and binds ATP through its Walker A motif. Unlike RAD51B and RAD51C it lacks the catalytic glutamate and is not an active ATPase within these complexes; it may instead regulate the ATPase of its partners. RAD51D is needed for homologous recombination repair of double-strand breaks and interstrand crosslinks, for slowing and reversing replication forks under stress, and for telomere maintenance, where it localises to telomeres and prevents telomere erosion and end-to-end fusions. The XRCC2-RAD51D subcomplex interacts with BLM and stimulates BLM-mediated disruption of Holliday junction-like structures in vitro. Rad51d loss is embryonic lethal in mice and causes chromosome instability. Germline loss-of-function variants in RAD51D predispose to ovarian cancer and confer PARP-inhibitor sensitivity.

Existing Annotations Review

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. contributes_to correctly records that this is a complex-level activity.
Supporting Evidence:
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. contributes_to correctly records that this is a complex-level activity.
Supporting Evidence:
PMID:20207730
both complexes bind with exceptionally high specificity to the DNA junctions
GO:0000722 telomere maintenance via recombination
IMP
PMID:15109494
Telomere maintenance requires the RAD51D recombination/repai...
KEEP AS NON CORE
Summary: Telomere maintenance via recombination (IMP).
Reason: In telomerase-negative human cells, which maintain telomeres by recombination, RAD51D knockdown caused telomere erosion and fusions. This supports a recombination-based telomere role. Kept as non-core.
Supporting Evidence:
PMID:15109494
RAD51D was shown to localize to the telomeres of both meiotic and somatic cells
PMID:15109494
Inhibition of RAD51D synthesis in telomerase-negative immortalized human cells by siRNA also resulted in telomere erosion and chromosome fusion
GO:0000723 telomere maintenance
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: Telomere maintenance (IBA).
Reason: RAD51D localises to telomeres, and its loss causes telomere shortening and end-to-end fusions in mouse and human cells. This is a genuine but secondary role of the HR machinery, not the defining function.
Supporting Evidence:
PMID:15109494
RAD51D was shown to localize to the telomeres of both meiotic and somatic cells
PMID:15109494
Inhibition of RAD51D synthesis in telomerase-negative immortalized human cells by siRNA also resulted in telomere erosion and chromosome fusion
GO:0000723 telomere maintenance
IEA
GO_REF:0000120
KEEP AS NON CORE
Summary: Telomere maintenance (IEA).
Reason: RAD51D localises to telomeres, and its loss causes telomere shortening and end-to-end fusions in mouse and human cells. This is a genuine but secondary role of the HR machinery, not the defining function.
Supporting Evidence:
PMID:15109494
RAD51D was shown to localize to the telomeres of both meiotic and somatic cells
PMID:15109494
Inhibition of RAD51D synthesis in telomerase-negative immortalized human cells by siRNA also resulted in telomere erosion and chromosome fusion
GO:0000723 telomere maintenance
IMP
PMID:15109494
Telomere maintenance requires the RAD51D recombination/repai...
KEEP AS NON CORE
Summary: Telomere maintenance (IMP).
Reason: RAD51D localises to telomeres, and its loss causes telomere shortening and end-to-end fusions in mouse and human cells. This is a genuine but secondary role of the HR machinery, not the defining function.
Supporting Evidence:
PMID:15109494
RAD51D was shown to localize to the telomeres of both meiotic and somatic cells
PMID:15109494
Inhibition of RAD51D synthesis in telomerase-negative immortalized human cells by siRNA also resulted in telomere erosion and chromosome fusion
GO:0000724 double-strand break repair via homologous recombination
IBA
GO_REF:0000033
ACCEPT
Summary: RAD51D functions in DSB repair via homologous recombination (IBA).
Reason: Central role. BCDX2 acts between BRCA2 and RAD51 recruitment, and the RAD51D-XRCC2 interaction is required for HR. Pathogenic RAD51D variants in the DNA-binding and ATP-binding core abolish HR.
Supporting Evidence:
PMID:23149936
the BCDX2 complex acts downstream of BRCA2 recruitment but upstream of Rad51 recruitment
PMID:30836272
the interaction of RAD51D with XRCC2 is required for DSB repair
PMID:41542474
variants in the DNA-binding or ATPase core most severely compromise HR
GO:0000724 double-strand break repair via homologous recombination
IMP
PMID:23149936
Rad51 paralog complexes BCDX2 and CX3 act at different stage...
ACCEPT
Summary: RAD51D functions in DSB repair via homologous recombination (IMP).
Reason: Central role. BCDX2 acts between BRCA2 and RAD51 recruitment, and the RAD51D-XRCC2 interaction is required for HR. Pathogenic RAD51D variants in the DNA-binding and ATP-binding core abolish HR.
Supporting Evidence:
PMID:23149936
the BCDX2 complex acts downstream of BRCA2 recruitment but upstream of Rad51 recruitment
PMID:30836272
the interaction of RAD51D with XRCC2 is required for DSB repair
PMID:41542474
variants in the DNA-binding or ATPase core most severely compromise HR
GO:0000781 chromosome, telomeric region
IDA
PMID:15109494
Telomere maintenance requires the RAD51D recombination/repai...
KEEP AS NON CORE
Summary: Chromosome, telomeric region (IDA).
Reason: Telomeric localisation of RAD51D is shown directly by immunofluorescence, EM and ChIP. It is a real but secondary location relative to the core HR function.
Supporting Evidence:
PMID:15109494
RAD51D was shown to localize to the telomeres of both meiotic and somatic cells
GO:0000781 chromosome, telomeric region
IEA
GO_REF:0000120
KEEP AS NON CORE
Summary: Chromosome, telomeric region (IEA).
Reason: Telomeric localisation of RAD51D is shown directly by immunofluorescence, EM and ChIP. It is a real but secondary location relative to the core HR function.
Supporting Evidence:
PMID:15109494
RAD51D was shown to localize to the telomeres of both meiotic and somatic cells
GO:0003677 DNA binding
IEA
GO_REF:0000002
ACCEPT
Summary: DNA binding (IEA).
Reason: Accurate general term; the more specific ssDNA and four-way-junction binding terms are annotated separately.
Supporting Evidence:
PMID:10871607
the purified RAD51L3 protein possesses single-stranded DNA binding activity and DNA-stimulated ATPase activity
GO:0003677 DNA binding
TAS
PMID:9570954
Identification, characterization, and genetic mapping of Rad...
ACCEPT
Summary: DNA binding (TAS).
Reason: Accurate general term; the more specific ssDNA and four-way-junction binding terms are annotated separately.
Supporting Evidence:
PMID:10871607
the purified RAD51L3 protein possesses single-stranded DNA binding activity and DNA-stimulated ATPase activity
GO:0003697 single-stranded DNA binding
IBA
GO_REF:0000033
ACCEPT
Summary: Single-stranded DNA binding (IBA).
Reason: Purified RAD51D binds ssDNA (PMID:10871607). Cryo-EM shows that the RAD51D N-terminal domain contributes to ssDNA-binding specificity of BCDX2 (PMID:37344589).
Supporting Evidence:
PMID:10871607
the purified RAD51L3 protein possesses single-stranded DNA binding activity and DNA-stimulated ATPase activity
PMID:37344589
The structures reveal how the amino-terminal domains of RAD51B, RAD51C and RAD51D participate in inter-subunit interactions that underpin complex formation and ssDNA-binding specificity
GO:0003697 single-stranded DNA binding
IDA
PMID:10871607
The RAD51 family member, RAD51L3, is a DNA-stimulated ATPase...
ACCEPT
Summary: Single-stranded DNA binding (IDA).
Reason: Purified RAD51D binds ssDNA (PMID:10871607). Cryo-EM shows that the RAD51D N-terminal domain contributes to ssDNA-binding specificity of BCDX2 (PMID:37344589).
Supporting Evidence:
PMID:10871607
the purified RAD51L3 protein possesses single-stranded DNA binding activity and DNA-stimulated ATPase activity
PMID:37344589
The structures reveal how the amino-terminal domains of RAD51B, RAD51C and RAD51D participate in inter-subunit interactions that underpin complex formation and ssDNA-binding specificity
GO:0005515 protein binding
IPI
PMID:10749867
Evidence for simultaneous protein interactions between human...
REMOVE
Summary: IPI protein binding between RAD51D and XRCC2 (PMID:10749867), from a targeted interaction study.
Reason: GO:0005515 protein binding is uninformative as a molecular function. This interaction with another RAD51 paralog reflects RAD51D'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:10871607
The RAD51 family member, RAD51L3, is a DNA-stimulated ATPase...
REMOVE
Summary: IPI protein binding between RAD51D and XRCC2 (PMID:10871607), from a targeted interaction study.
Reason: GO:0005515 protein binding is uninformative as a molecular function. This interaction with another RAD51 paralog reflects RAD51D'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 RAD51D and RAD51B (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 RAD51D'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 RAD51D 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 RAD51D'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 RAD51D and XRCC2 (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 RAD51D'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 RAD51D and RAD51B (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 RAD51D'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 RAD51D 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 RAD51D'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 RAD51D and XRCC2 (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 RAD51D'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:12975363
Functional interaction between the Bloom's syndrome helicase...
REMOVE
Summary: IPI protein binding between RAD51D and XRCC2 (PMID:12975363), from a targeted interaction study.
Reason: GO:0005515 protein binding is uninformative as a molecular function. This interaction with another RAD51 paralog reflects RAD51D'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:12975363
Functional interaction between the Bloom's syndrome helicase...
REMOVE
Summary: IPI protein binding between RAD51D and BLM (PMID:12975363), from a targeted interaction study.
Reason: GO:0005515 protein binding is uninformative. The RAD51D-BLM interaction is functionally relevant: XRCC2-RAD51D stimulates BLM disruption of 4-way junctions through it (PMID:12975363). GO has no specific molecular function that captures this, and the stimulation is a property of the XRCC2-RAD51D subcomplex, so it is recorded as a suggested question rather than as a replacement term.
GO:0005515 protein binding
IPI
PMID:16710300
Sws1 is a conserved regulator of homologous recombination in...
REMOVE
Summary: IPI protein binding between RAD51D and XRCC2 (PMID:16710300), from a targeted interaction study.
Reason: GO:0005515 protein binding is uninformative as a molecular function. This interaction with another RAD51 paralog reflects RAD51D'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:21516116
Next-generation sequencing to generate interactome datasets.
REMOVE
Summary: IPI protein binding between RAD51D and Q13422 (PMID:21516116), 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:21516116
Next-generation sequencing to generate interactome datasets.
REMOVE
Summary: IPI protein binding between RAD51D and Q9Y2J4 (PMID:21516116), 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:21965664
hSWS1Β·SWSAP1 is an evolutionarily conserved complex required...
REMOVE
Summary: IPI protein binding between RAD51D 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 RAD51D 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 RAD51D'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 RAD51D and XRCC2 (PMID:25416956), from a high-throughput interactome screen.
Reason: GO:0005515 protein binding is uninformative as a molecular function. This interaction with another RAD51 paralog reflects RAD51D'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 RAD51D and P19012 (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:25416956
A proteome-scale map of the human interactome network.
REMOVE
Summary: IPI protein binding between RAD51D and Q13422 (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:25416956
A proteome-scale map of the human interactome network.
REMOVE
Summary: IPI protein binding between RAD51D and Q6P1W5 (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:25416956
A proteome-scale map of the human interactome network.
REMOVE
Summary: IPI protein binding between RAD51D and Q8IYX8-2 (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:25416956
A proteome-scale map of the human interactome network.
REMOVE
Summary: IPI protein binding between RAD51D and Q8TBB1 (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:25416956
A proteome-scale map of the human interactome network.
REMOVE
Summary: IPI protein binding between RAD51D and Q9BRK4 (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:25416956
A proteome-scale map of the human interactome network.
REMOVE
Summary: IPI protein binding between RAD51D and Q9BVG8 (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:25416956
A proteome-scale map of the human interactome network.
REMOVE
Summary: IPI protein binding between RAD51D and Q9GZV8 (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:25416956
A proteome-scale map of the human interactome network.
REMOVE
Summary: IPI protein binding between RAD51D and Q9UKT9 (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:25416956
A proteome-scale map of the human interactome network.
REMOVE
Summary: IPI protein binding between RAD51D and Q9Y2J4-4 (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:25910212
Widespread macromolecular interaction perturbations in human...
REMOVE
Summary: IPI protein binding between RAD51D and F5H3M2 (PMID:25910212), 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:25910212
Widespread macromolecular interaction perturbations in human...
REMOVE
Summary: IPI protein binding between RAD51D and XRCC2 (PMID:25910212), from a high-throughput interactome screen.
Reason: GO:0005515 protein binding is uninformative as a molecular function. This interaction with another RAD51 paralog reflects RAD51D'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:25910212
Widespread macromolecular interaction perturbations in human...
REMOVE
Summary: IPI protein binding between RAD51D and P19012 (PMID:25910212), 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:25910212
Widespread macromolecular interaction perturbations in human...
REMOVE
Summary: IPI protein binding between RAD51D and Q13422-7 (PMID:25910212), 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:25910212
Widespread macromolecular interaction perturbations in human...
REMOVE
Summary: IPI protein binding between RAD51D and Q5JST6 (PMID:25910212), 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:25910212
Widespread macromolecular interaction perturbations in human...
REMOVE
Summary: IPI protein binding between RAD51D and Q6P1W5 (PMID:25910212), 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:25910212
Widespread macromolecular interaction perturbations in human...
REMOVE
Summary: IPI protein binding between RAD51D and Q6P2R3 (PMID:25910212), 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:25910212
Widespread macromolecular interaction perturbations in human...
REMOVE
Summary: IPI protein binding between RAD51D and Q8IYA8 (PMID:25910212), 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:25910212
Widespread macromolecular interaction perturbations in human...
REMOVE
Summary: IPI protein binding between RAD51D and Q8N5R6 (PMID:25910212), 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:25910212
Widespread macromolecular interaction perturbations in human...
REMOVE
Summary: IPI protein binding between RAD51D and Q8TBB1 (PMID:25910212), 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:25910212
Widespread macromolecular interaction perturbations in human...
REMOVE
Summary: IPI protein binding between RAD51D and Q9BRK4 (PMID:25910212), 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:25910212
Widespread macromolecular interaction perturbations in human...
REMOVE
Summary: IPI protein binding between RAD51D and Q9UKT9 (PMID:25910212), 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:25910212
Widespread macromolecular interaction perturbations in human...
REMOVE
Summary: IPI protein binding between RAD51D and Q9Y2J4 (PMID:25910212), 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 RAD51D and XRCC2 (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 RAD51D'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:31515488
Extensive disruption of protein interactions by genetic vari...
REMOVE
Summary: IPI protein binding between RAD51D and XRCC2 (PMID:31515488), from a high-throughput interactome screen.
Reason: GO:0005515 protein binding is uninformative as a molecular function. This interaction with another RAD51 paralog reflects RAD51D'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:31515488
Extensive disruption of protein interactions by genetic vari...
REMOVE
Summary: IPI protein binding between RAD51D and P19012 (PMID:31515488), 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:31515488
Extensive disruption of protein interactions by genetic vari...
REMOVE
Summary: IPI protein binding between RAD51D and Q13422 (PMID:31515488), 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:31515488
Extensive disruption of protein interactions by genetic vari...
REMOVE
Summary: IPI protein binding between RAD51D and Q9BVG8 (PMID:31515488), 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:31515488
Extensive disruption of protein interactions by genetic vari...
REMOVE
Summary: IPI protein binding between RAD51D and Q9UKT9 (PMID:31515488), 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:31515488
Extensive disruption of protein interactions by genetic vari...
REMOVE
Summary: IPI protein binding between RAD51D and Q9Y2J4 (PMID:31515488), 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 RAD51D and B2RXF5 (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 RAD51D and XRCC2 (PMID:32296183), from a high-throughput interactome screen.
Reason: GO:0005515 protein binding is uninformative as a molecular function. This interaction with another RAD51 paralog reflects RAD51D'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 RAD51D and O60504 (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 RAD51D and O75031 (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 RAD51D and O75558 (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 RAD51D and P15884-3 (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 RAD51D and P48059-3 (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 RAD51D and P57678 (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 RAD51D and Q04864-2 (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 RAD51D and Q08117-2 (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 RAD51D and Q14142 (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 RAD51D and Q53FD0-2 (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 RAD51D and Q5RL73 (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 RAD51D and Q5W5X9-3 (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 RAD51D 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 RAD51D and Q6NX45 (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 RAD51D and Q6P1L6 (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 RAD51D and Q8IYA8 (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 RAD51D and Q8ND90 (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 RAD51D and Q8NI38 (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 RAD51D and Q8WUT1 (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 RAD51D and Q96N21 (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 RAD51D and Q9BRK4 (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 RAD51D and Q9BVG8-5 (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 RAD51D and Q9H079 (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 RAD51D and Q9H0A9-2 (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 RAD51D and Q9NQX0 (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 RAD51D and Q9NRD5 (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 RAD51D and Q9UK58 (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 RAD51D and Q9UKT9 (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 RAD51D and Q9UPT6 (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 RAD51D and Q9Y2B5 (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 RAD51D and Q9Y2J4 (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 RAD51D and RAD51B (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 RAD51D'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 RAD51D 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 RAD51D'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 RAD51D and XRCC2 (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 RAD51D'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 RAD51D and RAD51B (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 RAD51D'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 RAD51D and XRCC2 (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 RAD51D'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 RAD51D and RAD51B (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 RAD51D'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 RAD51D 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 RAD51D'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 RAD51D and XRCC2 (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 RAD51D'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: RAD51D binds ATP through Walker A K113/T114 and Walker B D206, as seen in cryo-EM structures, even though it does not hydrolyse it.
Supporting Evidence:
PMID:37344587
observed that RAD51D and XRCC2 bound ATP whereas RAD51C bound ADP
GO:0005634 nucleus
IEA
GO_REF:0000120
ACCEPT
Summary: Nucleus (IEA).
Reason: Consistent with RAD51D's nuclear role in homologous recombination.
GO:0005634 nucleus
TAS
PMID:9570954
Identification, characterization, and genetic mapping of Rad...
ACCEPT
Summary: Nucleus (TAS).
Reason: Consistent with RAD51D'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 RAD51D'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 RAD51D'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 RAD51D'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 RAD51D'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 RAD51D'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 RAD51D'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 RAD51D'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 RAD51D'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 RAD51D'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 RAD51D'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 RAD51D'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 RAD51D'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 RAD51D'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 RAD51D'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 RAD51D'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 RAD51D'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 RAD51D'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 RAD51D is required for fork slowing and reversal under replication stress.
Supporting Evidence:
PMID:20207730
both complexes bind with exceptionally high specificity to the DNA junctions
PMID:32669601
RAD51C and RAD51D downregulation by two independent siRNA sequences drastically impaired active fork slowing
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 RAD51D is required for fork slowing and reversal under replication stress.
Supporting Evidence:
PMID:20207730
both complexes bind with exceptionally high specificity to the DNA junctions
PMID:32669601
RAD51C and RAD51D downregulation by two independent siRNA sequences drastically impaired active fork slowing
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 RAD51D is required for fork slowing and reversal under replication stress.
Supporting Evidence:
PMID:20207730
both complexes bind with exceptionally high specificity to the DNA junctions
PMID:32669601
RAD51C and RAD51D downregulation by two independent siRNA sequences drastically impaired active fork slowing
GO:0005813 centrosome
IDA
PMID:21276791
Homologous recombination proteins are associated with centro...
KEEP AS NON CORE
Summary: Centrosome (IDA).
Reason: HR proteins, including RAD51 paralogs, co-localise with centrosomes. This is peripheral to the nuclear HR function and kept as non-core, consistent with the XRCC2 review.
Supporting Evidence:
PMID:21276791
XRCC2 and other HR proteins, including the key recombinase RAD51, co-localize with the centrosome
GO:0005813 centrosome
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: Centrosome (IEA).
Reason: HR proteins, including RAD51 paralogs, co-localise with centrosomes. This is peripheral to the nuclear HR function and kept as non-core, consistent with the XRCC2 review.
Supporting Evidence:
PMID:21276791
XRCC2 and other HR proteins, including the key recombinase RAD51, co-localize with the centrosome
GO:0005815 microtubule organizing center
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: Active in microtubule organizing center (IBA).
Reason: Based on the centrosome co-localisation of HR proteins (PMID:21276791). The functional significance is unclear and probably secondary to genome maintenance, so it is kept as non-core.
Supporting Evidence:
PMID:21276791
XRCC2 and other HR proteins, including the key recombinase RAD51, co-localize with the centrosome
GO:0006281 DNA repair
IEA
GO_REF:0000002
ACCEPT
Summary: DNA repair (IEA).
Reason: Correct general parent of the specific HR term.
GO:0006281 DNA repair
TAS
PMID:9570954
Identification, characterization, and genetic mapping of Rad...
ACCEPT
Summary: DNA repair (TAS).
Reason: Correct general parent of the specific HR 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:0007131 reciprocal meiotic recombination
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: Reciprocal meiotic recombination (IBA).
Reason: The IBA reflects a conserved meiotic role of RAD51 paralogs (C. elegans RFS-1 is a donor). RAD51D localises to meiotic telomeres, but Rad51d knockout mice die as embryos, so there is no direct mammalian meiotic phenotype. Retained as a plausible, non-core conserved role.
Supporting Evidence:
PMID:15109494
RAD51D was shown to localize to the telomeres of both meiotic and somatic cells
GO:0007131 reciprocal meiotic recombination
TAS
PMID:9570954
Identification, characterization, and genetic mapping of Rad...
KEEP AS NON CORE
Summary: Reciprocal meiotic recombination (TAS, gene discovery paper).
Reason: The discovery paper speculates about a meiotic role from homology and testis expression. Because an IBA independently supports a conserved meiotic role, this is kept as non-core rather than flagged, but the TAS itself provides no experimental support.
Supporting Evidence:
PMID:9570954
it is likely that Rad51d is part of a complex of proteins required for DNA repair and meiotic recombination
GO:0008094 ATP-dependent activity, acting on DNA
IBA
GO_REF:0000033
MARK AS OVER ANNOTATED
Summary: ATP-dependent activity, acting on DNA (IBA; PANTHER node seeded by human RAD51D itself).
Reason: The IBA rests on the older report that isolated RAD51D is a DNA-stimulated ATPase. Two later cryo-EM studies of BCDX2 and X3CDX2 give target-specific evidence of divergence: RAD51D binds ATP but lacks the catalytic glutamate conserved in RAD51, RAD51B and RAD51C, so it is catalytically inactive in both complexes. A deep mutational scan suggests that RAD51D restrains, rather than provides, BCDX2 ATPase activity. ATP-driven catalysis is the property of RAD51B and RAD51C in this complex. RAD51D's ATP binding is captured by GO:0005524.
Propagation Review
Root cause: SOURCE WEAK OR INFERRED
Failure modes: PSEUDO OR SUBACTIVITY LOSS
Sources checked:
PANTHER:PTN000534427 SOURCE WEAK OR INFERRED
Ancestral node carrying the ATPase IBD. Its only listed experimental descendant evidence is human RAD51D itself (an isolated-protein ATPase assay, PMID:10871607); later structures show the RAD51D site is non-catalytic.
UniProtKB:O75771 SOURCE WEAK OR INFERRED
Target's own IDA (PMID:10871607) is contradicted by cryo-EM evidence that RAD51D lacks the catalytic glutamate (PMID:37344587, PMID:41196948).
Supporting Evidence:
PMID:37344587
These glutamates are not conserved in RAD51D or XRCC2 explaining their inability to promote ATP hydrolysis while retaining nucleotide binding
PMID:41196948
RAD51D and XRCC2 were both bound to ATP, as observed in the RAD51B complex, but neither is catalytically active due to the absence of an otherwise conserved catalytic glutamate residue
PMID:41542474
the primary function of RAD51D is to slow the ATPase activity of BCDX2
GO:0008094 ATP-dependent activity, acting on DNA
IDA
PMID:10871607
The RAD51 family member, RAD51L3, is a DNA-stimulated ATPase...
MARK AS OVER ANNOTATED
Summary: ATP-dependent activity, acting on DNA (IDA): purified RAD51D reported as a DNA-stimulated ATPase.
Reason: The original report (abstract only in cache) measured DNA-stimulated ATPase activity in purified RAD51D, which is experimental evidence. Later structural work shows RAD51D lacks the catalytic glutamate and is ATP-bound but catalytically inactive in BCDX2 and X3CDX2. The genetic data on the Walker A lysine conflict: human RAD51D K113 mutants complemented MMC sensitivity of hamster rad51d CHO cells efficiently (PMID:16717288), whereas mouse Rad51d K113R/K113A mutants lost most ICL-repair capacity in MEFs (PMID:16236763), which may reflect nucleotide binding (needed for RAD51C association) rather than hydrolysis. Neither study measures RAD51D catalysis directly. The activity measured in isolation may reflect low intrinsic or contaminating activity; the original data are not removed as wrong, but assigning a catalytic ATP-driven activity to RAD51D overstates its role, since within its physiological complexes ATP hydrolysis is carried out by RAD51B and RAD51C. Marked as over-annotated (consistent with the IBA row) and not used in the core functions.
Supporting Evidence:
PMID:10871607
the purified RAD51L3 protein possesses single-stranded DNA binding activity and DNA-stimulated ATPase activity
PMID:37344587
These glutamates are not conserved in RAD51D or XRCC2 explaining their inability to promote ATP hydrolysis while retaining nucleotide binding
PMID:41196948
RAD51D and XRCC2 were both bound to ATP, as observed in the RAD51B complex, but neither is catalytically active due to the absence of an otherwise conserved catalytic glutamate residue
GO:0033063 Rad51B-Rad51C-Rad51D-XRCC2 complex
IBA
GO_REF:0000033
ACCEPT
Summary: RAD51D is a subunit of the BCDX2 complex (IBA).
Reason: Core, well-established membership, shown by co-purification and cryo-EM. RAD51D bridges RAD51C and XRCC2 within the tetramer.
Supporting Evidence:
PMID:11751635
one contains RAD51B, RAD51C, RAD51D, and XRCC2 (defined as BCDX2)
PMID:10871607
the interaction between RAD51L3 and XRCC2 is direct
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: RAD51D is a subunit of the BCDX2 complex (IDA).
Reason: Core, well-established membership, shown by co-purification and cryo-EM. RAD51D bridges RAD51C and XRCC2 within the tetramer.
Supporting Evidence:
PMID:11751635
one contains RAD51B, RAD51C, RAD51D, and XRCC2 (defined as BCDX2)
PMID:10871607
the interaction between RAD51L3 and XRCC2 is direct
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: RAD51D is a subunit of the BCDX2 complex (IPI).
Reason: Core, well-established membership, shown by co-purification and cryo-EM. RAD51D bridges RAD51C and XRCC2 within the tetramer.
Supporting Evidence:
PMID:11751635
one contains RAD51B, RAD51C, RAD51D, and XRCC2 (defined as BCDX2)
PMID:10871607
the interaction between RAD51L3 and XRCC2 is direct
PMID:37344587
RAD51C-RAD51D-XRCC2 mimics three RAD51 protomers aligned within a nucleoprotein filament, whereas RAD51B is highly dynamic
GO:0042148 DNA strand invasion
IBA
GO_REF:0000033
ACCEPT
Summary: DNA strand invasion (IBA).
Reason: Purified XRCC2-RAD51D catalyses homologous pairing between ssDNA and dsDNA. In cells, RAD51D is part of X3CDX2, which caps RAD51 filaments and promotes homologous pairing and strand exchange. RAD51D therefore contributes to the strand-invasion step, although RAD51 is the main recombinase.
Supporting Evidence:
PMID:11834724
complex catalyzed homologous pairing between single-stranded and double-stranded DNA
PMID:41196948
the XRCC3 complex stably caps the 5' termini of RAD51 filaments to promote homologous pairing
PMID:42020761
enhances RAD51-ssDNA filament assembly, and promotes strand exchange on RPA-coated ssDNA
GO:0042148 DNA strand invasion
IDA
PMID:11834724
Homologous pairing and ring and filament structure formation...
ACCEPT
Summary: DNA strand invasion (IDA).
Reason: Purified XRCC2-RAD51D catalyses homologous pairing between ssDNA and dsDNA. In cells, RAD51D is part of X3CDX2, which caps RAD51 filaments and promotes homologous pairing and strand exchange. RAD51D therefore contributes to the strand-invasion step, although RAD51 is the main recombinase.
Supporting Evidence:
PMID:11834724
complex catalyzed homologous pairing between single-stranded and double-stranded DNA
PMID:41196948
the XRCC3 complex stably caps the 5' termini of RAD51 filaments to promote homologous pairing
PMID:42020761
enhances RAD51-ssDNA filament assembly, and promotes strand exchange on RPA-coated ssDNA
GO:0043015 gamma-tubulin binding
IDA
PMID:21276791
Homologous recombination proteins are associated with centro...
UNDECIDED
Summary: Gamma-tubulin binding (IDA).
Reason: The cached abstract reports centrosome co-localisation of XRCC2 and other HR proteins but describes no direct RAD51D-gamma-tubulin binding experiment. The curator presumably used full-text data (for example co-immunoprecipitation) that cannot be checked here. Left undecided rather than removed.
Supporting Evidence:
PMID:21276791
XRCC2 and other HR proteins, including the key recombinase RAD51, co-localize with the centrosome
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: BCDX2 increases the number and length of RAD51 nucleoprotein filaments. GO:0000730 DNA recombinase assembly describes this precisely, whereas supramolecular fiber organization is a generic parent. The same replacement is made in the RAD51C, RAD51B 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
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).
Reason: This is an over-propagation of a RecA/RAD51-family ATPase or damage-sensor function. RAD51D is not an active ATPase in its complexes and has no documented damage-recognition or signalling activity; its role is as a mediator subunit that promotes RAD51 filament assembly and capping. The same call is made in the RAD51C and XRCC2 reviews.
Supporting Evidence:
PMID:37344587
These glutamates are not conserved in RAD51D or XRCC2 explaining their inability to promote ATP hydrolysis while retaining nucleotide binding
PMID:41196948
RAD51D and XRCC2 were both bound to ATP, as observed in the RAD51B complex, but neither is catalytically active due to the absence of an otherwise conserved catalytic glutamate residue
GO:0140664 ATP-dependent DNA damage sensor activity
IMP
PMID:16717288
Disparate requirements for the Walker A and B ATPase motifs ...
MARK AS OVER ANNOTATED
Summary: ATP-dependent DNA damage sensor activity (IMP): Walker A/B mutants of human RAD51D tested for complementation of rad51d CHO cells.
Reason: The paper (full text) shows that the Walker B motif, but not the Walker A ATP-binding lysine, is needed for RAD51D's interactions with XRCC2 and RAD51C and for mitomycin C resistance. It does not test damage recognition or a signalling response, and the dispensability of motif A argues against an ATP-driven sensor activity. The authors propose bipartite ATPase sites formed with partner paralogs, which later structures confirmed, with RAD51D itself non-catalytic. The data support RAD51D's role in HR (captured by GO:0000724 and the NEW ICL-repair row) but not this molecular function.
Supporting Evidence:
PMID:16717288
a functional Walker B motif, but not A motif, is necessary for RAD51D's interactions with other paralogs and for efficient HRR
PMID:16717288
We present a model in which ATPase sites are formed in a bipartite manner between RAD51D and other RAD51 paralogs
GO:0031297 replication fork processing
IMP
PMID:32669601
Sequential role of RAD51 paralog complexes in replication fo...
NEW
Summary: RAD51D is required for active slowing and reversal of stressed replication forks (siRNA and knockout in U2OS cells).
Reason: Fork remodelling is a distinct, well-documented role of BCDX2 that is not captured by any existing RAD51D annotation. RAD51D is one of the paralogs tested most directly. The trigger review also assigns DX2 to stabilising FBH1-remodelled forks and to ATR-dependent control of fork progression. Purified BCDX2 has no fork-reversal activity itself, so the broader GO:0031297 is used rather than GO:0071932 replication fork reversal. BCDX2 participates by building and stabilising the RAD51 filament that remodels and protects the fork. Comparator: RAD51C carries GO:0031297 by IDA.
Supporting Evidence:
PMID:32669601
RAD51C and RAD51D downregulation by two independent siRNA sequences drastically impaired active fork slowing
PMID:32669601
we indeed confirmed that downregulation of RAD51C and RAD51D, but not of XRCC3, markedly impairs CPT-induced replication fork reversal
PMID:37843130
BCDX2 significantly synergizes with RAD51 to protect DNA against attack by the nucleases MRE11 and EXO1
GO:0036297 interstrand cross-link repair
IMP
PMID:16717288
Disparate requirements for the Walker A and B ATPase motifs ...
NEW
Summary: Human RAD51D complements the mitomycin C (interstrand crosslink) hypersensitivity of rad51d-knockout CHO cells, and Walker B mutants do not.
Reason: Repair of interstrand crosslinks by homologous recombination is a well-evidenced RAD51D function, shown by complementation in hamster and mouse rad51d-deficient cells. The two complementation studies disagree on whether the Walker A lysine is required (dispensable in hamster CHO cells, PMID:16717288; required in mouse MEFs, PMID:16236763; the conflict is recorded on the PMID:16236763 reference), but both show that RAD51D itself is needed for ICL repair, which is all this term asserts. Within the ICL pathway, RAD51D performs the RAD51-loading step of the HR stage, so it participates in the process. The same NEW term is added in the sibling RAD51C and XRCC2 reviews.
Supporting Evidence:
PMID:16717288
Although A-motif mutants complement very efficiently, B-motif mutants do not
PMID:16236763
The K113R and K113A mutants demonstrated a respective 96 and 83% decrease in repair capacity relative to wild-type

Core Functions

As a subunit of BCDX2, RAD51D forms the DX2 half with XRCC2. RAD51C-RAD51D-XRCC2 mimics a short RAD51 filament, and the complex binds ssDNA through the N-terminal domains and stimulates nucleation and extension of RAD51 filaments on RPA-coated ssDNA. This happens downstream of BRCA2 and upstream of RAD51 loading, in homologous recombination repair of DNA double-strand breaks and interstrand crosslinks. RAD51D binds but does not hydrolyse ATP, and may regulate the RAD51B-RAD51C ATPase.

Supporting Evidence:
  • PMID:37344587
    RAD51C-RAD51D-XRCC2 mimics three RAD51 protomers aligned within a nucleoprotein filament, whereas RAD51B is highly dynamic
  • PMID:37344587
    BCDX2 stimulates the nucleation and extension of RAD51
  • PMID:37344589
    The structures reveal how the amino-terminal domains of RAD51B, RAD51C and RAD51D participate in inter-subunit interactions that underpin complex formation and ssDNA-binding specificity
  • PMID:23149936
    the BCDX2 complex acts downstream of BRCA2 recruitment but upstream of Rad51 recruitment
  • PMID:41542474
    we identify the RAD51D-RAD51C interface within the BCDX2 complex as essential for regulating its ATPase activity

The RAD51D-XRCC2 subcomplex also joins RAD51C-XRCC3 to form X3CDX2. It remodels an autoinhibited RAD51-XRCC3-RAD51C assembly, and the resulting complex caps the 5' ends of RAD51 filaments, stabilising them and promoting homologous pairing and strand exchange. The isolated XRCC2-RAD51D complex can itself catalyse homologous pairing in vitro. No molecular function is asserted for this role. XRCC3 is the subunit that contacts RAD51, and RAD51-XRCC3-RAD51C stimulates strand exchange without RAD51D-XRCC2, so DNA strand exchange activator activity (GO:0140619, contributes_to) is assigned to XRCC3 only. X3CDX2 stimulates strand invasion more strongly than CX3, so RAD51D-XRCC2 may add to the activity, but no assay separates its own contribution.

Supporting Evidence:
  • PMID:41196948
    the XRCC3 complex stably caps the 5' termini of RAD51 filaments to promote homologous pairing
  • PMID:42020761
    the RAD51D-XRCC2 paralog complex remodels RAD51-X3C into a pentameric RAD51-X3CDX2 assembly
  • PMID:11834724
    complex catalyzed homologous pairing between single-stranded and double-stranded DNA
  • PMID:42020761
    RAD51–X3C displayed significantly enhanced DNA strand exchange activity over RAD51 alone across the protein concentrations tested

Within BCDX2, RAD51D binds replication-fork and Holliday-junction DNA. It is required for active fork slowing and RAD51-dependent fork reversal under replication stress, and BCDX2 works with RAD51 filaments to protect reversed forks from nucleolytic degradation.

Supporting Evidence:
  • PMID:20207730
    both complexes bind with exceptionally high specificity to the DNA junctions
  • PMID:32669601
    RAD51C and RAD51D downregulation by two independent siRNA sequences drastically impaired active fork slowing
  • PMID:37843130
    BCDX2 significantly synergizes with RAD51 to protect DNA against attack by the nucleases MRE11 and EXO1

References

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Suggested Questions for Experts

Q: GO has a cellular component term for BCDX2 (GO:0033063) and for CX3 (GO:0033065), but none for the XRCC3-RAD51C-RAD51D-XRCC2 (X3CDX2) complex now shown structurally and biochemically to cap RAD51 filaments. Should a new complex term be created so that RAD51D's membership in both tetramers can be recorded?

Q: Does RAD51D's non-catalytic ATP binding regulate ATP hydrolysis by RAD51C across the RAD51C-RAD51D interface, as the deep mutational scan proposes? Can the earlier report of intrinsic DNA-stimulated ATPase activity in isolated RAD51D be reconciled with the structural data?

Q: Is the telomere-protection role of RAD51D a specialised function at t-loops or telomere replication forks, or a general consequence of HR deficiency at hard-to-replicate regions?

Q: Does the RAD51D-BLM interaction, which lets XRCC2-RAD51D stimulate BLM-mediated junction disruption in vitro, operate in cells during late HR or fork restart? Would it warrant a specific molecular-function annotation such as an activator of helicase activity?

Suggested Experiments

Experiment: Measure ATP turnover by reconstituted BCDX2 and X3CDX2 carrying RAD51D variants at the RAD51C interface or Walker motifs, together with RAD51 filament assembly and capping in single-molecule assays.

Hypothesis: RAD51D variants that accelerate the complex ATPase impair RAD51 filament assembly, consistent with RAD51D acting as a brake on RAD51C-driven ATP hydrolysis.

Type: biochemical reconstitution

Experiment: Separation-of-function RAD51D mutants that block X3CDX2 formation but preserve BCDX2 (or the reverse), tested for DR-GFP HR, fork reversal, fork restart and telomere stability in RAD51D-knockout cells.

Hypothesis: BCDX2 and X3CDX2 contribute separable RAD51D functions: early filament assembly and fork reversal versus filament capping and fork restart.

Type: genetic complementation

πŸ“š Additional Documentation

Notes

(RAD51D-notes.md)

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