Affinage

RAD51D

DNA repair protein RAD51 homolog 4 · UniProt O75771

Length
328 aa
Mass
35.0 kDa
Annotated
2026-06-10
79 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAD51D is a RecA/RAD51-family DNA repair protein that is essential for homologous recombination (HR)-mediated repair of DNA double-strand breaks and for the maintenance of genomic stability and normal mammalian development (PMID:15781618, PMID:10705376). It is itself a single-stranded DNA-binding protein with DNA-stimulated ATPase activity, and forms a direct heterodimer with XRCC2 that catalyzes homologous pairing and assembles into ring and filamentous structures on ssDNA (PMID:10871607, PMID:11834724). RAD51D operates within the heterotetrameric BCDX2 complex (RAD51B-RAD51C-RAD51D-XRCC2), which preferentially binds branched DNA and nucleates and extends RAD51 filaments on ssDNA through coupled ATPase activities, with RAD51C-RAD51D-XRCC2 mimicking three RAD51 protomers in the nascent filament; the same RAD51C-RAD51D-XRCC2 module is shared with a distinct XRCC3-containing complex that caps the 5' filament terminus to promote homologous pairing (PMID:15141025, PMID:37344587, PMID:41196948). Within these complexes RAD51D's Walker B ATPase motif and its N-terminal domain mediate the XRCC2 and RAD51C interactions required for efficient HR, and its RAD51C interface tunes BCDX2 ATPase kinetics to license RAD51 filament assembly (PMID:16717288, PMID:21111057, PMID:30836272). RAD51D is required to recruit RAD51 to damage sites and to suppress chromosome instability, mutation, and gene amplification through error-free recombination, and it acts downstream of MLH1-dependent mismatch repair to resolve recombinogenic intermediates generated by O6-methylguanine and thiopurine lesions (PMID:15781618, PMID:16522646, PMID:20133210, PMID:21205838). Beyond DSB repair, RAD51D localizes to telomeres and protects telomeric 3' overhangs against attrition and end-to-end fusions (PMID:15109494, PMID:28945288). Its activity is controlled post-translationally by RNF138-mediated ubiquitination, which promotes RAD51D recruitment and HR, and translationally by m6A-dependent YTHDF3 activity (PMID:27161866, PMID:36380687). Loss of RAD51D function shifts repair toward error-prone single-strand annealing and end-joining, sensitizes cells to PARP inhibition, and clinical missense variants that disrupt the RAD51D-XRCC2 interface impair HR and confer PARP inhibitor sensitivity (PMID:28646019, PMID:27924006, PMID:21822267).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2000 High

    Establishing that RAD51D is a bona fide RAD51-family enzyme answered whether this paralog had intrinsic DNA-handling activity rather than being a passive structural protein.

    Evidence Recombinant protein purification with in vitro ATPase and ssDNA-binding assays plus co-immunoprecipitation with XRCC2

    PMID:10871607

    Open questions at the time
    • Did not show how RAD51D activity contributes within a multi-protein complex
    • No structural basis for ssDNA recognition
  2. 2000 High

    Knockout established that RAD51D is non-redundantly required for viability and recombinational repair, setting its biological essentiality.

    Evidence Gene-targeted mouse knockout with embryo phenotyping and primary fibroblast culture

    PMID:10705376

    Open questions at the time
    • Embryonic lethality obscured the molecular repair defect
    • p53-null rescue needed to study cells
  3. 2002 High

    Demonstrating that the XRCC2-RAD51D complex catalyzes homologous pairing and forms filaments showed it behaves as a recombination mediator at the biochemical level.

    Evidence Co-expressed purified complex in homologous pairing assays and electron microscopy

    PMID:11834724

    Open questions at the time
    • Activity studied as a dimer rather than the full paralog complex
    • Relationship to RAD51 filament formation not addressed
  4. 2004 High

    Placing RAD51D in the BCDX2 complex with defined branched-DNA preference clarified the substrate specificity of the paralog assembly.

    Evidence Competitive DNA-binding and strand-annealing assays with purified BCDX2

    PMID:15141025

    Open questions at the time
    • Mechanism of RAD51 filament nucleation not yet resolved
    • Stoichiometric architecture of the complex unknown
  5. 2004 High

    Identifying telomere localization and protection extended RAD51D's role beyond DSB repair to genome end maintenance.

    Evidence Immunofluorescence, EM, ChIP, knockout MEFs and siRNA depletion with cytogenetics

    PMID:15109494

    Open questions at the time
    • Whether telomere protection uses the same complexes as DSB repair unclear
    • Direct binding to telomeric DNA not demonstrated
  6. 2005 High

    Showing reduced RAD51 focus formation and chromosome instability in knockout cells established RAD51D as required upstream of RAD51 recruitment for HR.

    Evidence Knockout mouse MEFs with survival, cytogenetic, RAD51 foci and sister chromatid exchange assays

    PMID:15781618

    Open questions at the time
    • Molecular step at which RAD51 loading fails not defined
    • Centrosome fragmentation mechanism unexplained
  7. 2006 High

    Mapping Walker A and Walker B motif requirements distinguished the ATPase residues needed for catalysis versus paralog interactions, refining the bipartite-ATPase model.

    Evidence Active-site mutagenesis with complementation in deficient cells and yeast hybrid interaction assays

    PMID:16236763 PMID:16717288

    Open questions at the time
    • Bipartite ATPase sites inferred but not structurally confirmed at this stage
    • Single-lab interaction assays
  8. 2006 High

    Quantifying mutation and gene-amplification rates in RAD51D-deficient cells established that its HR function is error-free and suppresses multiple classes of genetic alteration.

    Evidence Knockout CHO cells with hprt mutation, gene amplification and cytogenetic assays

    PMID:16522646

    Open questions at the time
    • Did not separate DSB repair from replication-associated functions
    • Pathway redirection upon loss not characterized
  9. 2009 Medium

    Identifying SFPQ as a direct partner and synthetic-lethal interactor broadened the interaction network supporting RAD51D-dependent HR.

    Evidence Proteomics, direct interaction assay, siRNA depletion and chromosome instability/cohesion assays

    PMID:20813759

    Open questions at the time
    • RAD51D-specific contribution to SFPQ functions not isolated
    • Single-lab synthetic lethality
  10. 2010 High

    Solving the NMR structure of the N-terminal domain defined the ssDNA-binding surface and its discrimination against duplex and Holliday-junction DNA.

    Evidence NMR structure determination with EMSA and NMR titration

    PMID:21111057

    Open questions at the time
    • Structure of full-length protein and ATPase core absent
    • Domain studied in isolation from complex partners
  11. 2010 High

    Genetic epistasis with MLH1 placed RAD51D-mediated HR downstream of mismatch repair in resolving lesion-induced recombinogenic intermediates.

    Evidence Trp53/Mlh1/Rad51d knockout MEFs with MNNG and 6-thioguanine sensitivity, gamma-H2AX, cell cycle and cytogenetic assays

    PMID:20133210 PMID:21205838

    Open questions at the time
    • Identity of the recombinogenic intermediate not biochemically defined
    • Does not address spontaneous DSB repair pathway order
  12. 2016 High

    Identifying RNF138-mediated ubiquitination established a post-translational control layer that governs RAD51D recruitment and HR efficiency.

    Evidence Co-IP, ubiquitination assays, RING mutagenesis, siRNA depletion, RAD51 foci and HR reporter assays with live-cell imaging

    PMID:27161866 PMID:27195665

    Open questions at the time
    • How ubiquitination mechanistically promotes recruitment unresolved
    • Deubiquitinase counter-regulation unknown
  13. 2017 High

    Showing that RAD51D loss redirects repair toward SSA and end-joining explained the large-deletion signature of RAD51D deficiency.

    Evidence Endogenous-locus HR reporter with I-SceI-induced DSBs and deletion mapping in deficient CHO cells

    PMID:27924006

    Open questions at the time
    • Determinants of SSA-versus-NHEJ choice not defined
    • Generalizability beyond CHO model untested
  14. 2017 Medium

    Functional characterization of clinical variants linked the RAD51D-XRCC2 interface directly to HR competence and PARP inhibitor response.

    Evidence Case-control genotyping with yeast two-hybrid, HR and PARP inhibitor sensitivity assays in patient-derived cells

    PMID:28646019

    Open questions at the time
    • Single-lab interface mapping
    • Structural basis of the interface disruption not shown
  15. 2019 High

    Defining the functional isoform and characterizing Walker-A-proximal cancer variants tied the RAD51D-XRCC2 interaction to DSB repair at endogenous loci.

    Evidence Yeast two/three-hybrid, co-IP and sister chromatid recombination HR reporter in knockout U2OS cells with complementation

    PMID:30836272

    Open questions at the time
    • Mechanism by which interface loss blocks RAD51 loading not resolved
    • Isoform regulation in vivo unclear
  16. 2023 High

    Cryo-EM of BCDX2 revealed that RAD51C-RAD51D-XRCC2 mimics RAD51 protomers and that coupled ATPase activities drive RAD51 filament nucleation and extension, providing the structural mechanism for paralog-mediated HR.

    Evidence Cryo-EM, AlphaFold2 modeling, structural proteomics, single-molecule and biochemical filament/ATPase assays

    PMID:37344587

    Open questions at the time
    • Dynamics of RAD51B within the complex incompletely resolved
    • Telomere-specific complex composition not addressed
  17. 2022 Medium

    Identifying the HNF1alpha/YTHDF3 axis showed RAD51D is regulated translationally via m6A, adding a layer controlling its protein output.

    Evidence HNF1alpha and YTHDF3 depletion/overexpression, protein-versus-mRNA western blotting, irradiation assays in cervical cancer cells

    PMID:36380687

    Open questions at the time
    • Direct m6A sites on RAD51D mRNA not mapped
    • Single cancer context
  18. 2026 High

    Cryo-EM resolved two distinct paralog complexes sharing RAD51C-RAD51D-XRCC2, assigning the RAD51B complex to dynamic filament assembly and the XRCC3 complex to 5'-terminal capping for homologous pairing.

    Evidence Cryo-EM with biochemical filament assembly and single-molecule visualization

    PMID:41196948

    Open questions at the time
    • Functional switching between the two complexes in cells not shown
    • RAD51D-specific role in each complex not isolated
  19. 2026 Medium

    A saturation-scale variant screen mapped HR-critical residues to the DNA-binding/ATPase core and proposed that RAD51D primarily slows BCDX2 ATPase to time RAD51 assembly.

    Evidence Multiplex saturation genome editing assay of 6,888 variants with orthogonal HR, biochemical and ATPase assays (preprint)

    PMID:41542474

    Open questions at the time
    • ATPase-slowing model awaits independent confirmation
    • Variant effects measured in a single assay system
    • Preprint

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the two paralog complexes are dynamically partitioned in cells and how RAD51D's distinct DSB-repair versus telomere-protection functions are mechanistically coordinated remains open.
  • No in-cell switch between BCDX2 and XRCC3 complexes defined
  • Telomeric complex composition and recruitment unmapped
  • Coupling of post-translational/translational regulation to complex assembly unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 3 GO:0003677 DNA binding 2 GO:0060090 molecular adaptor activity 2 GO:0140097 catalytic activity, acting on DNA 2 GO:0016787 hydrolase activity 1
Localization
GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 2
Pathway
R-HSA-73894 DNA Repair 3 R-HSA-1640170 Cell Cycle 2
Partners
BLMBRCA2RAD51BRAD51CRNF138SFPQXRCC2XRCC3
Complex memberships
BCDX2 (RAD51B-RAD51C-RAD51D-XRCC2)XRCC3 complex (XRCC3-RAD51C-RAD51D-XRCC2)

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 RAD51D (RAD51L3) possesses single-stranded DNA binding activity and DNA-stimulated ATPase activity, consistent with Walker box motifs in its sequence, and forms a direct heterodimeric complex with XRCC2 in human cells, as demonstrated by purification of the recombinant protein and co-immunoprecipitation. Protein purification, in vitro ATPase assay, ssDNA binding assay, co-immunoprecipitation The Journal of biological chemistry High 10871607
2002 The purified human XRCC2·RAD51D complex catalyzes homologous pairing between single-stranded and double-stranded DNA, forms multimeric ring structures in the absence of DNA, and assembles into filamentous structures on ssDNA, similar to other homologous pairing proteins. Recombinant protein co-expression and purification in E. coli, in vitro homologous pairing assay, electron microscopy The Journal of biological chemistry High 11834724
2003 BLM helicase makes a direct physical interaction with RAD51D (RAD51L3) through the N-terminal domain of BLM, and the RAD51D-XRCC2 complex stimulates BLM to disrupt synthetic 4-way (Holliday junction) structures in a manner dependent on direct physical association between BLM and RAD51D. Protein purification, in vitro Holliday junction disruption assay, co-immunoprecipitation, domain-mapping with BLM truncation mutants The Journal of biological chemistry High 12975363
2004 The RAD51B-RAD51C-RAD51D-XRCC2 (BCDX2) complex preferentially binds to branched DNA substrates (Y-shaped DNA and synthetic Holliday junctions) over linear ssDNA or dsDNA, and catalyzes strand-annealing between long complementary ssDNA molecules. Competitive DNA-binding assays with purified BCDX2 complex using seven DNA substrate types, strand-annealing assay Nucleic acids research High 15141025
2004 RAD51D localizes to telomeres in both meiotic and somatic cells; Rad51d-deficient mouse embryonic fibroblasts exhibit telomeric DNA repeat shortening, elevated chromosomal end-to-end fusions, and siRNA-mediated depletion in telomerase-negative human cells also causes telomere erosion and chromosome fusion, establishing a dual role for RAD51D in DNA double-strand break repair and telomere maintenance. Immunofluorescence labeling, electron microscopy, chromatin immunoprecipitation, siRNA knockdown, cytogenetic analysis Cell High 15109494
2005 Rad51d-deficient mouse embryonic fibroblasts (in p53-null background) are sensitive to DNA-damaging agents, exhibit extensive chromosome instability (aneuploidy, fragments, complex rearrangements), increased centrosome fragmentation, reduced radiation-induced RAD51 focus formation, and fail to increase sister chromatid exchange in response to mitomycin C, demonstrating RAD51D is required for RAD51 recruitment and homologous recombination repair. Knockout mouse model, cell survival assays, cytogenetic analysis, immunofluorescence for RAD51 foci, sister chromatid exchange assay Cancer research High 15781618
2005 The Walker A (ATP binding) motif of RAD51D is required for efficient homologous recombination repair of DNA interstrand crosslinks; Walker A mutations K113R and K113A reduce repair capacity by 83–96% and diminish interaction with RAD51C (8-fold reduction) while retaining interaction with XRCC2. Site-directed mutagenesis, complementation in Rad51d-deficient MEFs, yeast two-hybrid analysis Mutagenesis High 16236763
2006 The Walker B ATPase motif of RAD51D is required for interactions with XRCC2 and RAD51C and for efficient homologous recombinational repair, whereas the Walker A motif is not required for these interactions or complementation of crosslink sensitivity; ATPase sites are proposed to form in a bipartite manner between RAD51D and other paralogs. ATPase motif mutagenesis, complementation in rad51d knockout CHO cells, yeast two- and three-hybrid assays, co-immunoprecipitation Nucleic acids research High 16717288
2006 RAD51D-deficient CHO cells exhibit a 12-fold increased rate of hprt mutation and 4–10-fold increased gene amplification at dhfr and CAD loci, as well as elevated spontaneous chromatid breaks, demonstrating that RAD51D-mediated homologous recombination acts in an error-free manner to suppress multiple classes of genetic alterations. Rad51d knockout CHO cells, hprt mutation assay, gene amplification assay, cytogenetic analysis Nucleic acids research High 16522646
2009 SFPQ/PSF interacts directly with RAD51D (and also RAD51C and XRCC2) as identified by proteomics; depletion of both SFPQ and RAD51D results in a synthetic lethal relationship. SFPQ deficiency alone leads to sister chromatid cohesion defects and chromosome instability, and mediates homology-directed DNA repair. Proteomics screen, direct protein interaction assay, siRNA knockdown, cell viability assay, chromosome instability analysis, sister chromatid cohesion assay Nucleic acids research Medium 20813759
2009 The RAD51D E233G variant decreases interaction with RAD51C by ~2-fold while maintaining normal XRCC2 interaction, increases cellular resistance to multiple DNA-damaging agents, reduces anaphase bridge index, and increases proliferation. Molecular modeling suggests glutamic acid-233 forms a salt bridge with lysine-23 in the RAD51D N-terminal domain that is disrupted by the glycine substitution. Yeast two-hybrid, complementation in Rad51d-deficient MEFs, cell survival assays, molecular modeling Pharmacogenetics and genomics Medium 19033885
2010 RAD51D protects cells from MLH1-dependent cytotoxicity induced by O6-methylguanine: Rad51d-deficient cells are 5.3-fold sensitive to MNNG, with G2/M arrest and apoptosis; loss of Mlh1 alleviates this sensitivity, demonstrating that RAD51D-mediated homologous recombination acts downstream of MMR to resolve recombinogenic intermediates created by MMR recognition of O6-meG:T mismatches. Genetic epistasis using Rad51d/Mlh1/Trp53 triple-knockout MEFs, MNNG sensitivity assay, γ-H2AX measurement, cell cycle analysis, apoptosis assay DNA repair High 20133210
2010 The NMR solution structure of the human RAD51D N-terminal domain (residues 1-83) consists of four short helices flanked by N- and C-terminal tails, with the N-terminal tail fixed by hydrophobic interactions (Leu4/Thr27, Leu4/Val28, Val6/Ile17). The domain preferentially binds ssDNA over dsDNA and does not bind mobile Holliday junctions, with NMR titration identifying positively charged and hydrophobic surface residues for ssDNA binding. NMR structure determination, EMSA (ssDNA vs dsDNA binding), NMR titration The international journal of biochemistry & cell biology High 21111057
2011 RAD51D-deficient cells are extremely sensitive to 6-thioguanine; this sensitivity is almost completely rescued by deletion of Mlh1, establishing that RAD51D-mediated homologous recombination acts downstream of MLH1-dependent mismatch repair to resolve 6-thioG-induced recombinogenic lesions. Rad51d-deficient cells also show markedly increased triradial and quadriradial chromosomal aberrations after 6-thioG treatment. Genetic epistasis with Rad51d/Mlh1 double-knockout cells, 6-thioG sensitivity assay, cytogenetic analysis Molecular cancer research : MCR High 21205838
2016 RNF138 E3 ubiquitin ligase directly interacts with and ubiquitinates RAD51D; RNF138 depletion increases RAD51D protein stability, reduces RAD51 focus formation, and causes sensitivity to DNA-damaging agents and chromosome instability. The RNF138 RING finger domain is required for RAD51D ubiquitination, and RNF138 presence enhances the RAD51D-XRCC2 interaction. Co-immunoprecipitation, ubiquitination assay, siRNA depletion, RAD51 foci assay, RING domain mutagenesis, yeast three-hybrid DNA repair High 27161866
2016 Ubiquitylation of Rad51D by RNF138 promotes homologous recombination repair: RNF138 is recruited to DNA damage sites via its zinc finger domains, is phosphorylated by ATM at Ser124 (though this phosphorylation is dispensable for recruitment), and directly interacts with RAD51D; RNF138 depletion delays and destabilizes RAD51D recruitment to damage sites and reduces HR efficiency. Live cell imaging, co-immunoprecipitation, siRNA depletion, HR reporter assay, comet assay PloS one Medium 27195665
2017 The RAD51D missense variant p.S207L disrupts the RAD51D-XRCC2 protein-protein interaction and impairs homologous recombination, conferring PARP inhibitor sensitivity; this highlights the RAD51D-XRCC2 interaction as critical for HR function and tumor suppression. Case-control genotyping, yeast two-hybrid interaction assay, HR assay, PARP inhibitor sensitivity assay in patient-derived cells Cancer research Medium 28646019
2017 RAD51D deficiency shifts DSB repair from homologous recombination-mediated gene conversion toward single-strand annealing (SSA) and end-joining pathways, resulting in an exceptionally high frequency of large chromosomal deletions surrounding site-specific DSBs; deletions near the break are due to NHEJ while larger deletions use SSA. HR reporter assay at endogenous Aprt locus, I-SceI-induced DSBs, loss-of-function RAD51D-deficient CHO cells, deletion mapping Nucleic acids research High 27924006
2017 RAD51D is required for maintaining telomeric 3' overhangs; Rad51d-deficient cells show increased γ-H2AX localization at telomeres following 6-thioguanine treatment and undergo mitotic catastrophe (failed division and restitution) leading to multinucleated cell formation. γ-H2AX foci assay with telomere co-localization, live-cell imaging of mitotic catastrophe, Rad51d-deficient cells Environmental and molecular mutagenesis Medium 28945288
2019 RAD51D isoform 1 is the functional isoform for HR; isoform 4 (large N-terminal deletion including Walker A motif) and isoform 6 (alternate N-terminal exon) are non-functional. Cancer-associated mutations G96C and G107V near/within the Walker A motif independently disrupt RAD51D interaction with XRCC2, reduce HR efficiency in a sister chromatid recombination reporter assay, and the RAD51D-XRCC2 interaction is required for DSB repair. Yeast two-hybrid and three-hybrid, co-immunoprecipitation, sister chromatid recombination HR reporter assay in RAD51D knockout U2OS cells, functional complementation DNA repair High 30836272
2023 Cryo-EM, AlphaFold2 modeling, and structural proteomics reveal that in the BCDX2 complex, RAD51C-RAD51D-XRCC2 mimics three RAD51 protomers aligned within a nucleoprotein filament while RAD51B is highly dynamic. BCDX2 stimulates nucleation and extension of RAD51 filaments on ssDNA in reactions dependent on the coupled ATPase activities of RAD51B and RAD51C, establishing that BCDX2 orchestrates RAD51 assembly for replication fork protection and double-strand break repair. Cryo-electron microscopy, AlphaFold2 structural modeling, structural proteomics, single-molecule analysis, biochemical RAD51 filament assembly assays, ATPase assays Nature High 37344587
2022 YTHDF3 mediates translation of RAD51D mRNA in an m6A-dependent manner downstream of HNF1α transcriptional upregulation of YTHDF3; HNF1α positively regulates RAD51D at the protein level but not mRNA level, and this HNF1α/YTHDF3/RAD51D axis promotes radioresistance in cervical cancer cells. Depletion/overexpression of HNF1α and YTHDF3, western blotting (protein vs. mRNA level distinction), in vitro and in vivo irradiation assays The FEBS journal Medium 36380687
2026 Cryo-EM reveals two distinct heterotetrameric RAD51 paralog complexes: RAD51B-RAD51C-RAD51D-XRCC2 (RAD51B complex) and XRCC3-RAD51C-RAD51D-XRCC2 (XRCC3 complex). The RAD51B complex promotes dynamic ATP hydrolysis-dependent RAD51 filament assembly, while the XRCC3 complex stably caps the 5' termini of RAD51 filaments to promote homologous pairing, with RAD51C-RAD51D-XRCC2 shared between both complexes. Cryo-electron microscopy, biochemical filament assembly assays, single-molecule visualization Science (New York, N.Y.) High 41196948
2026 A high-throughput multiplex assay of 6,888 RAD51D coding variants identifies that variants in the DNA-binding or ATPase core most severely compromise HR. The RAD51D-RAD51C interface within the BCDX2 complex is essential for regulating ATPase activity, and paradoxically, the primary function of RAD51D appears to be slowing the ATPase activity of BCDX2 to allow sufficient time for RAD51 filament assembly. Multiplex assay of variant effect (saturation genome editing), orthogonal HR and biochemical assays across 70 clinical variants, ATPase activity assays bioRxiv : the preprint server for biologypreprint Medium 41542474
2024 Using yeast two-hybrid and three-hybrid approaches, RAD51 paralogs (including RAD51D as part of BCDX2) interact with BRCA2 at two distinct hubs: the BRC repeats (BRC1-2) and the DNA binding domain. RAD51D is part of the BCDX2 complex that interacts with BRCA2 BRC repeats. Yeast two-hybrid, yeast three-hybrid, co-immunoprecipitation bioRxivpreprint Low bio_10.1101_2024.10.10.617680
2000 Rad51d-deficient mouse embryos die between 8.5–11.5 dpc with posterior truncation and developmental delay; embryonic fibroblasts cannot be propagated, demonstrating that RAD51D is essential for normal mammalian development, consistent with a role in recombinational DNA repair during mitosis. Gene targeting/knockout in mice, embryo phenotyping, primary fibroblast culture Genesis (New York, N.Y. : 2000) High 10705376
2011 RAD51D-deficient cells are sensitive to PARP inhibitor treatment, demonstrating that RAD51D function in homologous recombination is required for resistance to PARP inhibition. PARP inhibitor sensitivity assay in RAD51D-deficient cells (inferred from clinical genetics paper describing PARP inhibitor sensitivity in RAD51D-deficient cells) Nature genetics Medium 21822267
2009 Mouse RAD51D splice variant RAD51DDelta7b (deleted for residues 219–223) retains interaction with both RAD51C and XRCC2, while RAD51D+int3 retains interaction with XRCC2 only. The linker region (residues 54–77) of RAD51D was identified as a region mediating binding with XRCC2. None of the splice variants restore resistance to mitomycin C in Rad51d-deficient cells. Yeast two-hybrid, EGFP fusion localization, complementation assay, RT-PCR BMC molecular biology Medium 19327148

Source papers

Stage 0 corpus · 79 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Germline mutations in RAD51D confer susceptibility to ovarian cancer. Nature genetics 406 21822267
2017 Secondary Somatic Mutations Restoring RAD51C and RAD51D Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma. Cancer discovery 341 28588062
2015 Contribution of Germline Mutations in the RAD51B, RAD51C, and RAD51D Genes to Ovarian Cancer in the Population. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 258 26261251
2004 Telomere maintenance requires the RAD51D recombination/repair protein. Cell 175 15109494
2018 Cost-effectiveness of Population-Based BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2 Mutation Testing in Unselected General Population Women. Journal of the National Cancer Institute 153 29361001
2000 Midgestation lethality in mice deficient for the RecA-related gene, Rad51d/Rad51l3. Genesis (New York, N.Y. : 2000) 125 10705376
1998 Identification, characterization, and genetic mapping of Rad51d, a new mouse and human RAD51/RecA-related gene. Genomics 108 9570954
2010 The splicing-factor related protein SFPQ/PSF interacts with RAD51D and is necessary for homology-directed repair and sister chromatid cohesion. Nucleic acids research 103 20813759
2000 The RAD51 family member, RAD51L3, is a DNA-stimulated ATPase that forms a complex with XRCC2. The Journal of biological chemistry 92 10871607
2020 BRIP1, RAD51C, and RAD51D mutations are associated with high susceptibility to ovarian cancer: mutation prevalence and precise risk estimates based on a pooled analysis of ~30,000 cases. Journal of ovarian research 85 32359370
2013 Systematic screen identifies miRNAs that target RAD51 and RAD51D to enhance chemosensitivity. Molecular cancer research : MCR 83 24088786
2006 Repression of mutagenesis by Rad51D-mediated homologous recombination. Nucleic acids research 83 16522646
2005 Extensive chromosomal instability in Rad51d-deficient mouse cells. Cancer research 80 15781618
2003 Functional interaction between the Bloom's syndrome helicase and the RAD51 paralog, RAD51L3 (RAD51D). The Journal of biological chemistry 74 12975363
2004 Preferential binding to branched DNA strands and strand-annealing activity of the human Rad51B, Rad51C, Rad51D and Xrcc2 protein complex. Nucleic acids research 72 15141025
2022 Moderate penetrance genes complicate genetic testing for breast cancer diagnosis: ATM, CHEK2, BARD1 and RAD51D. Breast (Edinburgh, Scotland) 69 35772246
2002 Homologous pairing and ring and filament structure formation activities of the human Xrcc2*Rad51D complex. The Journal of biological chemistry 65 11834724
2023 Structure and function of the RAD51B-RAD51C-RAD51D-XRCC2 tumour suppressor. Nature 58 37344587
2022 Enhancing the BOADICEA cancer risk prediction model to incorporate new data on RAD51C, RAD51D, BARD1 updates to tumour pathology and cancer incidence. Journal of medical genetics 58 36162851
2006 Disparate requirements for the Walker A and B ATPase motifs of human RAD51D in homologous recombination. Nucleic acids research 51 16717288
2013 Roles of XRCC2, RAD51B and RAD51D in RAD51-independent SSA recombination. PLoS genetics 45 24278037
2012 A Finnish founder mutation in RAD51D: analysis in breast, ovarian, prostate, and colorectal cancer. Journal of medical genetics 41 22652533
2012 Mutation analysis of RAD51D in non-BRCA1/2 ovarian and breast cancer families. British journal of cancer 38 22415235
2022 YTHDF3 mediates HNF1α regulation of cervical cancer radio-resistance by promoting RAD51D translation in an m6A-dependent manner. The FEBS journal 32 36380687
2017 Functionally Null RAD51D Missense Mutation Associates Strongly with Ovarian Carcinoma. Cancer research 32 28646019
2013 Analysis of RAD51D in ovarian cancer patients and families with a history of ovarian or breast cancer. PloS one 31 23372765
2012 Loss of function germline mutations in RAD51D in women with ovarian carcinoma. Gynecologic oncology 31 22986143
2018 Associations between RAD51D germline mutations and breast cancer risk and survival in BRCA1/2-negative breast cancers. Annals of oncology : official journal of the European Society for Medical Oncology 28 30165555
2005 The ATPase motif in RAD51D is required for resistance to DNA interstrand crosslinking agents and interaction with RAD51C. Mutagenesis 26 16236763
2008 Genome integrity is regulated by the Caenorhabditis elegans Rad51D homolog rfs-1. Genetics 25 18458109
2014 About 1% of the breast and ovarian Spanish families testing negative for BRCA1 and BRCA2 are carriers of RAD51D pathogenic variants. International journal of cancer 23 24130102
2004 The variant E233G of the RAD51D gene could be a low-penetrance allele in high-risk breast cancer families without BRCA1/2 mutations. International journal of cancer 22 15170666
2009 The interaction profile of homologous recombination repair proteins RAD51C, RAD51D and XRCC2 as determined by proteomic analysis. Proteomics 21 19658102
2021 A decade of RAD51C and RAD51D germline variants in cancer. Human mutation 20 34923718
2019 RAD51D splice variants and cancer-associated mutations reveal XRCC2 interaction to be critical for homologous recombination. DNA repair 19 30836272
2016 The recombination mediator RAD51D promotes geminiviral infection. Virology 19 27018825
2021 Age of ovarian cancer diagnosis among BRIP1, RAD51C, and RAD51D mutation carriers identified through multi-gene panel testing. Journal of ovarian research 18 33926482
1999 Multiple alternative transcripts of the human homologue of the mouse TRAD/R51H3/RAD51D gene, a member of the rec A/RAD51 gene family. Biochemical and biophysical research communications 18 10092526
2017 The homologous recombination protein RAD51D protects the genome from large deletions. Nucleic acids research 17 27924006
2016 RNF138 interacts with RAD51D and is required for DNA interstrand crosslink repair and maintaining chromosome integrity. DNA repair 17 27161866
2010 RAD51D protects against MLH1-dependent cytotoxic responses to O(6)-methylguanine. DNA repair 17 20133210
2024 Human Fallopian Tube-Derived Organoids with TP53 and RAD51D Mutations Recapitulate an Early Stage High-Grade Serous Ovarian Cancer Phenotype In Vitro. International journal of molecular sciences 16 38255960
2021 RAD51D Aberrant Splicing in Breast Cancer: Identification of Splicing Regulatory Elements and Minigene-Based Evaluation of 53 DNA Variants. Cancers 16 34200360
2015 Mutation Analysis of the RAD51C and RAD51D Genes in High-Risk Ovarian Cancer Patients and Families from the Czech Republic. PloS one 14 26057125
2013 Hypermethylation of RAD51L3 and XRCC2 genes to predict late toxicity in chemoradiotherapy-treated cervical cancer patients. Folia biologica 14 24485306
2018 Mutational analysis of RAD51C and RAD51D genes in hereditary breast and ovarian cancer families from Murcia (southeastern Spain). European journal of medical genetics 13 29409816
2016 Ubiquitylation of Rad51d Mediated by E3 Ligase Rnf138 Promotes the Homologous Recombination Repair Pathway. PloS one 12 27195665
2018 Contribution of RAD51D germline mutations in breast and ovarian cancer in Greece. Journal of human genetics 10 30111881
2012 Uncoupling of RAD51 focus formation and cell survival after replication fork stalling in RAD51D null CHO cells. Environmental and molecular mutagenesis 10 22302683
2011 The homologous recombination protein RAD51D mediates the processing of 6-thioguanine lesions downstream of mismatch repair. Molecular cancer research : MCR 10 21205838
2022 The Genetic and Molecular Analyses of RAD51C and RAD51D Identifies Rare Variants Implicated in Hereditary Ovarian Cancer from a Genetically Unique Population. Cancers 9 35565380
2010 Structural and functional characterization of the N-terminal domain of human Rad51D. The international journal of biochemistry & cell biology 9 21111057
2009 Functional characterization and identification of mouse Rad51d splice variants. BMC molecular biology 9 19327148
2008 Germline mutations in RAD51, RAD51AP1, RAD51B, RAD51C,RAD51D, RAD52 and RAD54L do not contribute to familial chronic lymphocytic leukemia. Leukemia & lymphoma 9 18203022
2024 Germline testing of BRCA1, BRCA2, PALB2 and CHEK2 c.1100delC in 1514 triple negative familial and isolated breast cancers from a single centre, with extended testing of ATM, RAD51C and RAD51D in over 400. Journal of medical genetics 8 38123987
2023 RAD51D Secondary Mutation-Mediated Resistance to PARP-Inhibitor-Based Therapy in HGSOC. International journal of molecular sciences 8 37833926
2019 Association between polymorphisms in MicroRNA target sites of RAD51D genes and risk of hepatocellular carcinoma. Cancer medicine 8 30883040
2009 Functional characterization of the RAD51D E233G genetic variant. Pharmacogenetics and genomics 8 19033885
2009 Cisplatin resistance conferred by the RAD51D (E233G) genetic variant is dependent upon p53 status in human breast carcinoma cell lines. Molecular carcinogenesis 8 19347880
2007 The RAD51D E233G variant and breast cancer risk: population-based and clinic-based family studies of Australian women. Breast cancer research and treatment 8 18058226
2026 Cryo-electron microscopic visualization of RAD51 filament assembly and end-capping by XRCC3-RAD51C-RAD51D-XRCC2. Science (New York, N.Y.) 7 41196948
2004 Genomic structure and multiple alternative transcripts of the mouse TRAD/RAD51L3/RAD51D gene, a member of the recA/RAD51 gene family. Biochimica et biophysica acta 7 15297144
2023 RAD51C-RAD51D interplays with MSH5 and regulates crossover maturation in rice meiosis. The New phytologist 6 37430391
2022 Clinical characteristics and survival analysis of Chinese ovarian cancer patients with RAD51D germline mutations. BMC cancer 6 36544182
2021 Germline mutations in RAD51C and RAD51D and hereditary predisposition to ovarian cancer. Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti 5 33657816
2021 The RAD51D c.82G>A (p.Val28Met) variant disrupts normal splicing and is associated with hereditary ovarian cancer. Breast cancer research and treatment 4 33452952
2021 New germline mutations in BRCA1, ATM, MUTYH, and RAD51D genes in Tuvans early-onset breast cancer patients. Experimental oncology 4 33785725
2024 Germline Mutational Landscape and Novel Targetable RAD51D Variant in Chinese Patients With Ovarian Cancer. JCO global oncology 2 38905575
2024 Germline RAD51C and RAD51D Mutations in High-Risk Chinese Breast and/or Ovarian Cancer Patients and Families. Journal of personalized medicine 2 39202057
2022 Serous Tubal Intraepithelial Carcinoma in a Risk-reducing Salpingo-oophorectomy Specimen From a RAD51D Mutation Carrier: A Case Report. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 2 35149617
2022 Identification of new RAD51D-regulating microRNAs that also emerge as potent inhibitors of the Fanconi anemia/homologous recombination pathways. Human molecular genetics 2 35904444
2021 Retroperitoneal leiomyosarcoma in a female patient with a germline splicing variant RAD51D c.904-2A > T: a case report. Hereditary cancer in clinical practice 2 34838098
2009 RAD51D- and FANCG-dependent base substitution mutagenesis at the ATP1A1 locus in mammalian cells. Mutation research 2 19427512
2024 Four cancer cases with pathological germline variant RAD51D c.270_271dup. The journal of obstetrics and gynaecology research 1 39117461
2024 Marginal Contribution of Pathogenic RAD51D Germline Variants to Pakistani Early-Onset and Familial Breast/Ovarian Cancer Patients. Journal of cancer & allied specialties 1 39156943
2026 High-throughput mapping of 6,888 RAD51D variants identifies distinct biochemical functions needed for homologous recombination and olaparib response. bioRxiv : the preprint server for biology 0 41542474
2026 Whole Exome Sequencing Revealed Rare Variants in BRCA2, RAD51D, FANGC, CYP24A1 Genes in Breast/Ovarian Cancer Patients from a Small Buryat Ethnic Group. Asian Pacific journal of cancer prevention : APJCP 0 41660923
2024 Endometrial Cancer in a Family With RAD51D Gene Mutation. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 0 38661557
2017 Thiopurine-induced mitotic catastrophe in Rad51d-deficient mammalian cells. Environmental and molecular mutagenesis 0 28945288

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