Affinage

BRCA2

Breast cancer type 2 susceptibility protein · UniProt P51587

Length
3418 aa
Mass
384.2 kDa
Annotated
2026-06-09
100 papers in source corpus 27 papers cited in narrative 27 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

BRCA2 is a central mediator of homologous recombination (HR) that loads and stabilizes the RAD51 recombinase on resected DNA to drive error-free repair of double-strand breaks, with loss of function producing chromosomal instability, checkpoint defects, and crosslinker hypersensitivity (PMID:9660919, PMID:11756561). A large C-terminal domain binds single-stranded DNA through three OB folds (with an HTH motif implicated in dsDNA binding) and stimulates RAD51-mediated recombination in vitro (PMID:12228710). Full-length BRCA2 binds RAD51 and selectively assembles it onto ssDNA over dsDNA, displaces RPA, and stabilizes the resulting filament by blocking RAD51 ATP hydrolysis (PMID:20729832); at the molecular level it accelerates RAD51 nucleation on RPA-coated ssDNA to rates approaching those on naked ssDNA, overcoming the kinetic barrier RPA imposes (PMID:36976771). The eight BRC repeats engage RAD51 non-equivalently to control filament assembly versus disruption (PMID:15937124), while the C-terminal TR2 motif braces adjacent RAD51 protomers across the filament interface via an acidic-patch contact (PMID:37919288). BRCA2 is brought to damage sites through the BRCA1–PALB2 axis, which places BRCA1 upstream of BRCA2 in HR (PMID:19268590), and through FANCD2/Fanconi-pathway interactions that promote its chromatin loading (PMID:15199141, PMID:12915460). Beyond canonical HR, BRCA2 protects reversed replication forks from MRE11-, PTIP-, and RAD52-mediated nucleolytic degradation by assembling stable RAD51 filaments on regressed arms (PMID:29038466), and it limits DNA:RNA hybrid (R-loop) accumulation at breaks and at G/C-rich chromatin by recruiting RNase H2 in S/G2 phase (PMID:30560944, PMID:35715464). Its activity is governed by phosphoregulation and proteostasis: ATM/ATR phosphorylation recruits PP2A-B56 to promote RAD51 filament formation (PMID:34593815), a PLK1-T207 phosphorylation event builds a PP2A–BUBR1 complex required for mitotic chromosome alignment (PMID:32286328), DSS1 and ssDNA control BRCA2 oligomeric state (PMID:32609828), and reactive metabolites such as formaldehyde and methylglyoxal trigger its proteasomal degradation to cause transient functional haploinsufficiency and mutagenesis (PMID:28575672, PMID:38608703). BRCA2 additionally functions as a meiotic recombination mediator, stimulating DMC1 strand exchange through DMC1-preferring BRC repeats and acting within meiosis-specific complexes (PMID:26976601, PMID:31242413, PMID:32609828).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1998 High

    Established that BRCA2 is a nuclear protein physically and functionally linked to the recombination and tumor-suppression machinery, by showing in vivo complexes with RAD51 and p53 and a DNA-repair phenotype upon disruption.

    Evidence Co-IP and transcriptional reporter assays in human cells; murine Brca2 truncation with survival, cell-cycle, and cytogenetic readouts

    PMID:9660919 PMID:9811893

    Open questions at the time
    • Did not define the biochemical mechanism of RAD51 regulation
    • p53 transcriptional effect not mapped to a direct molecular activity
  2. 2002 High

    Defined the structural basis of BRCA2 DNA engagement by resolving the DSS1-bound C-terminal domain with three OB folds that bind ssDNA and demonstrating it stimulates RAD51 recombination in vitro.

    Evidence X-ray crystallography (apo and ssDNA-bound) with in vitro DNA-binding and recombination assays

    PMID:12228710

    Open questions at the time
    • Used a domain fragment rather than full-length protein
    • Did not show how RPA-coated ssDNA is handled in cells
  3. 2002 High

    Linked BRCA2 deficiency directly to RAD51 nuclear localization and genome stability by identifying BRCA2 as the XRCC11 gene and characterizing crosslinker sensitivity, checkpoint defects, and centrosome abnormalities.

    Evidence Chromosome and cDNA complementation of V-C8 hamster cells with survival, cytogenetic, and RAD51 localization assays

    PMID:11756561

    Open questions at the time
    • Did not separate HR from fork-protection contributions to instability
    • Centrosome phenotype mechanism unresolved
  4. 2005 Medium

    Resolved how the BRC repeats interface with RAD51 filaments, showing non-equivalent repeats that bind distinct RAD51 surfaces and can either nucleate or disrupt filaments depending on stoichiometry.

    Evidence Electron microscopy of RAD51-DNA filaments with BRC peptides plus interaction mapping

    PMID:15937124

    Open questions at the time
    • Used isolated BRC peptides rather than intact BRCA2
    • In vivo relevance of disruptive activity not established
  5. 2009 High

    Placed BRCA1 upstream of BRCA2 in the DNA-damage response by showing PALB2 bridges the two and is required for their concentration at damage sites and for HR.

    Evidence Reciprocal co-IP, siRNA depletion, laser-microirradiation focus recruitment, and HR reporter assay

    PMID:19268590

    Open questions at the time
    • Did not define structural detail of the PALB2-BRCA2 contact
    • Quantitative contribution of this axis to overall recruitment unclear
  6. 2010 High

    Provided definitive biochemical proof of BRCA2's mediator activity by purifying full-length human BRCA2 and showing it loads RAD51 onto ssDNA, displaces RPA, and stabilizes filaments by blocking ATP hydrolysis.

    Evidence Reconstitution with full-length purified BRCA2; binding, competition, RPA-displacement, and ATPase assays

    PMID:20729832

    Open questions at the time
    • Did not visualize nucleation kinetics at single-molecule resolution
    • Cellular regulation of this activity not addressed
  7. 2016 High

    Extended BRCA2 mediator function to meiosis by showing distinct BRC repeats prefer DMC1 and that full-length BRCA2 stimulates DMC1-mediated strand exchange.

    Evidence In vitro BRC-DMC1 binding and DMC1 strand-exchange assays with purified full-length BRCA2

    PMID:26976601

    Open questions at the time
    • Meiosis-specific cofactors not yet identified at this stage
    • In vivo meiotic requirement of specific repeats untested
  8. 2017 High

    Distinguished BRCA2's HR function from fork protection and connected its loss to replication stress and metabolite-driven degradation, defining how partial BRCA2 loss drives instability.

    Evidence DNA fiber spreading and EM of replication intermediates with genetic perturbation; CRISPR conditional knockout in mammary cells; aldehyde-induced proteolysis assays with RNase H1 rescue

    PMID:28575672 PMID:28904335 PMID:29038466

    Open questions at the time
    • Degradation machinery targeting BRCA2 not identified
    • Relative importance of HR vs fork protection may be context-dependent
  9. 2018 Medium

    Identified a non-canonical BRCA2 role in controlling R-loops at breaks by showing it recruits RNase H2 to DSBs in S/G2 phase.

    Evidence Co-IP, laser-microirradiation focus assay, and DRIP with cell-cycle staging

    PMID:30560944

    Open questions at the time
    • Single lab without reciprocal structural validation
    • How R-loop control feeds into repair efficiency not quantified
  10. 2020 Medium

    Revealed regulatory layers governing BRCA2 — mitotic PLK1 phosphorylation building a PP2A-BUBR1 complex for chromosome alignment, DSS1/ssDNA control of oligomerization, and dedicated meiotic complexes.

    Evidence In vitro phosphorylation, co-IP, phosphopeptide NMR, chromosome alignment assays; pulldown and EM of oligomeric states; co-IP and mouse knockouts for MEILB2/BRME1 and HSF2BP

    PMID:31242413 PMID:32286328 PMID:32345962 PMID:32609828

    Open questions at the time
    • Structural basis of full-length oligomerization unresolved
    • Crosstalk between mitotic and HR functions unclear
  11. 2021 High

    Connected damage signaling to RAD51 loading by showing ATM/ATR phosphorylation recruits PP2A-B56 to BRCA2 for efficient filament formation, with disruptive mutations conferring PARP-inhibitor sensitivity.

    Evidence Phosphoproteomics, reciprocal co-IP, HR assay, PARP inhibitor sensitivity, and motif mutagenesis

    PMID:34593815

    Open questions at the time
    • Precise dephosphorylation substrate of recruited PP2A-B56 not defined
    • Temporal ordering relative to PALB2-mediated recruitment unclear
  12. 2024 Medium

    Demonstrated that a glycolytic metabolite can transiently inactivate BRCA2 by proteolysis, generating cancer-associated mutational signatures in monoallelic-mutant cells without biallelic loss.

    Evidence Protein stability assays, mutational signature analysis, patient-derived organoids, and mouse models with proteasome rescue

    PMID:38608703

    Open questions at the time
    • Specific E3 ligase/proteolytic pathway not identified
    • In vivo frequency of this mechanism in tumorigenesis unquantified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse BRCA2 regulatory inputs (PALB2/FANCD2 recruitment, ATM/ATR-PP2A signaling, PLK1 mitotic phosphorylation, oligomerization, and metabolite-driven degradation) are integrated in time and space to coordinate HR, fork protection, R-loop control, and mitotic fidelity remains unresolved.
  • No unified structural model of full-length BRCA2 with its regulators
  • Mechanism switching between mitotic and meiotic functions undefined
  • Quantitative hierarchy of competing recruitment pathways unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0140096 catalytic activity, acting on a protein 3 GO:0003677 DNA binding 2
Localization
GO:0000228 nuclear chromosome 2 GO:0005694 chromosome 2 GO:0005634 nucleus 1
Pathway
R-HSA-73894 DNA Repair 4 R-HSA-1474165 Reproduction 3 R-HSA-69306 DNA Replication 3 R-HSA-1640170 Cell Cycle 2
Partners
DMC1DSS1FANCD2HSF2BPPALB2PLK1RAD51RNASEH2
Complex memberships
BRCA1-PALB2-BRCA2BRCA2-MEILB2-BRME1BRCA2-PLK1-PP2A-BUBR1BRCA2-PP2A-B56

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Crystal structure of a ~90 kDa BRCA2 C-terminal domain bound to DSS1 reveals three OB folds and a helix-turn-helix (HTH) motif; the domain binds single-stranded DNA (ssDNA) via the OB folds; the HTH motif is implicated in dsDNA binding; and this BRCA2 domain stimulates RAD51-mediated recombination in vitro. X-ray crystallography (3.1 Å apo structure; 3.5 Å ssDNA-bound structure), in vitro DNA-binding assays, in vitro RAD51 recombination stimulation assay Science High 12228710
2010 Full-length purified human BRCA2 binds RAD51 and promotes assembly of RAD51 onto ssDNA over dsDNA, displaces RPA from ssDNA, and stabilizes RAD51-ssDNA filaments by blocking ATP hydrolysis; BRCA2 does not anneal RPA-coated ssDNA, indicating it does not function in ssDNA-annealing repair pathways. Purification of full-length human BRCA2, in vitro RAD51 binding, ssDNA/dsDNA competition assays, RPA displacement assay, ATPase assay Nature High 20729832
2023 Cryo-EM structure and structure-guided mutagenesis reveal that the BRCA2 TR2 motif at the C-terminus binds across the protomer interface of the RAD51 nucleoprotein filament, acting as a molecular brace for adjacent RAD51 molecules and stabilizing the filament; TR2 targets an acidic-patch motif on human RAD51. Cryo-electron microscopy, structure-guided mutagenesis Nature Communications High 37919288
2023 Single-molecule visualization shows that BRCA2 accelerates RAD51 nucleation on RPA-coated ssDNA to rates approaching association with naked ssDNA, overcoming the kinetic barrier imposed by RPA; a dimer of RAD51 is minimally required for spontaneous nucleation; BRCA2 can chaperone a preassembled short RAD51 filament onto RPA-coated ssDNA. Microfluidics, single-molecule fluorescence microscopy, micromanipulation of individual DNA molecules Proceedings of the National Academy of Sciences High 36976771
2005 BRCA2 BRC repeats (BRC3 and BRC4) bind RAD51-DNA nucleoprotein filaments at low molar ratios, with BRC3 contacting the N-terminal domain of RAD51 and BRC4 contacting the nucleotide-binding core; at high concentrations the BRC repeats disrupt filaments. The eight BRC repeats are non-equivalent in their mode of RAD51 interaction. Electron microscopy of RAD51-DNA filaments incubated with BRC peptides, protein-protein interaction mapping Proceedings of the National Academy of Sciences Medium 15937124
2016 BRCA2 BRC repeats interact directly with the meiosis-specific recombinase DMC1; BRC1-3 bind RAD51 preferentially while BRC6-8 bind DMC1 preferentially; individual BRC repeats (except BRC4) stimulate DMC1-ssDNA complex formation; full-length BRCA2 stimulates DMC1-mediated DNA strand exchange between RPA-ssDNA and duplex DNA, identifying BRCA2 as a mediator of DMC1 recombination. In vitro BRC repeat-DMC1 binding assays, DNA strand exchange assay with purified full-length BRCA2, RPA-ssDNA competition assay Proceedings of the National Academy of Sciences High 26976601
1998 BRCA2 is a ~460 kDa nuclear phosphoprotein that forms in vivo complexes with both p53 and RAD51; exogenous BRCA2 expression inhibits p53 transcriptional activity, and RAD51 co-expression enhances this inhibitory effect. Co-immunoprecipitation from human cells, transient transfection/transcriptional reporter assays Proceedings of the National Academy of Sciences Medium 9811893
1998 Cells with a targeted truncation of murine Brca2 show proliferative impediment, G1 and G2/M arrest with elevated p53/p21, hypersensitivity to UV and MMS, spontaneous chromosomal breaks and aberrant chromatid exchanges, establishing Brca2 function in DNA repair. Mouse gene targeting (Brca2 truncation), colony survival assays, cell cycle analysis, cytogenetics Molecular Cell High 9660919
2009 BRCA1 associates with BRCA2 through PALB2/FANCN; in PALB2-deficient cells the BRCA1-BRCA2 interaction is abrogated; BRCA1 promotes concentration of PALB2 and BRCA2 at DNA-damage sites; the BRCA1-PALB2 interaction is required for homologous recombination repair, placing BRCA1 upstream of BRCA2 in the DNA-damage response. Co-immunoprecipitation, siRNA depletion, laser-microirradiation focus recruitment assay, HR reporter assay Current Biology High 19268590
2004 Monoubiquitination of FANCD2 (activated by DNA damage) is required for targeting FANCD2 to chromatin where it interacts with BRCA2 and promotes BRCA2 chromatin loading; the C-terminus of BRCA2 is required for functional colocalization of BRCA2 and FANCD2 in chromatin complexes. Chromatin fractionation, co-immunoprecipitation, immunofluorescence focus assays, complementation with wild-type BRCA2 cDNA in BRCA2-deficient cells Molecular and Cellular Biology High 15199141
2003 FANCG directly binds BRCA2 at two separate sites flanking the BRC repeats (by yeast two-hybrid); FANCG co-immunoprecipitates with BRCA2 from human cells and co-localizes with BRCA2 and RAD51 in nuclear foci after mitomycin C treatment. Yeast two-hybrid, co-immunoprecipitation, immunofluorescence co-localization Human Molecular Genetics Medium 12915460
2003 EMSY protein binds BRCA2 within an exon 3-encoded region deleted in cancer, silences the transcriptional activation potential of BRCA2 exon 3, associates with chromatin regulators HP1β and BS69, and localizes to sites of DNA repair following DNA damage. Co-immunoprecipitation/pulldown, transcriptional reporter assay, immunofluorescence Cell Medium 14651845
2002 BRCA2 deficiency in XRCC11-complementation group hamster cells (V-C8) causes radioresistant DNA synthesis (checkpoint defect), extreme sensitivity to interstrand crosslinking agents, chromosomal instability, abnormal centrosomes, and reduced nuclear localization of RAD51. Chromosome 13 complementation, Brca2 cDNA complementation, clonogenic survival assays, cytogenetics, immunofluorescence for Rad51 localization Molecular and Cellular Biology High 11756561
2017 Reversed replication forks are entry points for nucleolytic fork degradation in BRCA2-defective cells; MRE11, PTIP, and RAD52 promote stalled fork degradation and chromosomal breakage in BRCA2-deficient cells; impairing fork reversal prevents fork degradation but increases chromosomal breakage; BRCA2 assembles stable RAD51 nucleofilaments on regressed arms to protect them from degradation. DNA fiber spreading, direct visualization of replication intermediates (electron microscopy), genetic inactivation of fork-reversal and degradation factors Nature Communications High 29038466
2020 PLK1 phosphorylates BRCA2 at a conserved T207 site in mitosis, creating a PLK1 docking site; BRCA2 bound to PLK1 forms a complex with phosphatase PP2A and phosphorylated BUBR1; breast cancer variants S206C and T207A reduce BRCA2-PLK1 binding, destabilize this tetrameric complex, and cause unstable kinetochore-microtubule interactions, misaligned chromosomes, and aneuploidy. In vitro phosphorylation assay, co-immunoprecipitation, NMR structure of phosphopeptide, chromosomal alignment assays in cells expressing BRCA2 variants Nature Communications High 32286328
2021 ATM and ATR kinases phosphorylate a conserved region in BRCA2 in response to DSBs; these phosphorylations recruit the phosphatase PP2A-B56 to BRCA2 via a conserved binding motif; the BRCA2-PP2A-B56 complex is required for efficient RAD51 filament formation at DNA damage sites and HR-mediated repair; cancer-associated BRCA2 mutations that deregulate this interaction sensitize cells to PARP inhibition. Phosphoproteomics, co-immunoprecipitation, HR assay, PARP inhibitor sensitivity assay, mutagenesis of PP2A-binding motif Nature Communications High 34593815
2018 BRCA2 directly interacts with RNase H2 and mediates RNase H2 localization to DSBs specifically in S/G2 phase, controlling DNA:RNA hybrid (R-loop) levels at DSBs; damage-induced lncRNAs contribute to recruitment of BRCA1, BRCA2, and RAD51 to DSBs without affecting DNA-end resection. Co-immunoprecipitation, laser-microirradiation and focus assay, DNA:RNA hybrid immunoprecipitation (DRIP), cell-cycle-staged analysis Nature Communications Medium 30560944
2017 Formaldehyde selectively depletes BRCA2 via proteasomal degradation; heterozygous BRCA2 truncations sensitize cells to BRCA2 haploinsufficiency induced by formaldehyde or acetaldehyde, causing replication fork stalling, chromosomal aberrations, and R-loop accumulation; Ribonuclease H1 ameliorates these replication defects, linking BRCA2 inactivation to spontaneous mutagenesis via aberrant RNA-DNA hybrids. Western blot for BRCA2 protein levels after aldehyde treatment, proteasome inhibitor rescue, DNA fiber assay, cytogenetics, RNase H1 overexpression rescue Cell High 28575672
2019 HSF2BP interacts with a specific 68-amino acid region of BRCA2 (Gly2270–Thr2337, between BRC repeats and the DNA-binding domain) via armadillo repeats; this interaction is constitutive in mouse embryonic stem cells; Hsf2bp knockout mice are male infertile due to a severe HR defect during spermatogenesis. Co-immunoprecipitation, yeast two-hybrid domain mapping, mouse knockout, meiotic HR assay Cell Reports Medium 31242413
2020 BRCA2 forms a ternary complex with MEILB2 and BRME1 in meiosis; BRME1 stabilizes MEILB2 by preventing its self-association; BRCA2 binds the C-terminus of MEILB2; Brme1 knockout mice show defects in DSB repair, homolog synapsis, and crossover formation; ectopic expression of MEILB2-BRME1 in somatic cancer cells impairs mitotic HR. Co-immunoprecipitation, mouse knockout, immunofluorescence for DSB repair proteins, HR assay in somatic cells Nature Communications Medium 32345962
2020 DSS1 and ssDNA counteract BRCA2 oligomerization; three self-interacting regions and two types of self-association (N-to-C and N-to-N terminal) were identified; the N-to-C interaction is sensitive to DSS1 and ssDNA, while the N-to-N interaction is modulated by ssDNA; defining a regulatory mechanism for BRCA2 oligomeric state. Biochemical pulldown assays, electron microscopic imaging of BRCA2 complexes, domain mapping Nucleic Acids Research Medium 32609828
2022 ZFP281 interacts with BRCA2 and is required for BRCA2 recruitment to bivalent chromatin (with PRC2); depletion of ZFP281 or BRCA2 causes R-loop accumulation over bivalent regions and impairs DNA replication progression; ZFP281 cooperates with BRCA2 to prevent persistent R-loops at G/C-rich promoters. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), DRIP (DNA:RNA hybrid immunoprecipitation), DNA replication assay, siRNA depletion Nature Communications Medium 35715464
2024 The glycolytic metabolite methylglyoxal (MGO) triggers BRCA2 proteolysis, transiently disabling BRCA2 tumor suppressive functions in DNA repair and replication and causing functional haploinsufficiency; this generates a cancer-associated mutational signature (SBS) in non-malignant mammary cells without biallelic BRCA2 inactivation; BRCA2 monoallelic mutations predispose to these changes. Protein stability assays (western blot after MGO treatment), mutational signature analysis, patient-derived organoids, mouse models, proteasome inhibitor rescue Cell Medium 38608703
2008 PARP-1 binds a silencer region (-582 to -516) of the BRCA2 promoter in vitro and in vivo and down-regulates BRCA2 expression; PARP-1 inhibitors or PARP-1 siRNA increase endogenous BRCA2 expression; inhibition of PARP-1 activity reduces histone H3K9 acetylation and blocks PARP-1 binding to the BRCA2 promoter. Affinity purification and mass spectrometry, EMSA (gel shift), antibody super-shift, chromatin immunoprecipitation (ChIP), PARP-1 siRNA knockdown, PARP inhibitor treatment Journal of Biological Chemistry Medium 18990703
2005 BRCA2 binds and stabilizes MAGE-D1 protein; BRCA2 and MAGE-D1 synergistically suppress cell proliferation independently of the p53 pathway; MAGE-D1 expression is required for BRCA2-mediated suppression of cell proliferation (shown by RNAi), establishing MAGE-D1 as a downstream effector of BRCA2 in growth suppression. Co-immunoprecipitation, RNAi knockdown, cell proliferation assay, western blot Cancer Research Medium 15930293
2006 FANCC gene disruption in brca2ΔCTD (C-terminal domain truncation) cells reveals epistasis between FANCC and the BRCA2 CTD for X-ray sensitivity; however, combined fancc/brca2ΔCTD cells show additive sensitivity to cisplatin and increased MMC-induced chromosomal aberrations relative to either single mutant, indicating the FA pathway has a CTD-independent role in interstrand crosslink repair separate from BRCA2-RAD51-mediated HR. Conditional gene targeting (brca2ΔCTD), FANCC disruption, clonogenic survival assays, cytogenetics Journal of Biological Chemistry Medium 16687415
2017 In non-transformed human mammary epithelial cells, BRCA2 loss causes replication stress associated with DNA under-replication, leading to mitotic abnormalities, 53BP1 nuclear body formation in the subsequent G1 phase, and G1 arrest; the HR function of BRCA2 (not stalled-fork protection) is primarily responsible for supporting cell viability in this context. CRISPR-Cas9 conditional BRCA2 knockout in human mammary epithelial cells, DNA fiber assay, immunofluorescence (53BP1 nuclear bodies, γH2AX), cell cycle analysis Nature Communications High 28904335

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell 1340 11832208
2007 Meta-analysis of BRCA1 and BRCA2 penetrance. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 1339 17416853
2011 BRCA1 and BRCA2: different roles in a common pathway of genome protection. Nature reviews. Cancer 1124 22193408
1996 The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds. Nature genetics 696 8589730
2004 BRCA1 and BRCA2: 1994 and beyond. Nature reviews. Cancer 692 15343273
2002 BRCA2 function in DNA binding and recombination from a BRCA2-DSS1-ssDNA structure. Science (New York, N.Y.) 576 12228710
2010 Purified human BRCA2 stimulates RAD51-mediated recombination. Nature 559 20729832
1998 Involvement of Brca2 in DNA repair. Molecular cell 527 9660919
2009 PALB2 links BRCA1 and BRCA2 in the DNA-damage response. Current biology : CB 443 19268590
2003 EMSY links the BRCA2 pathway to sporadic breast and ovarian cancer. Cell 343 14651845
2017 Replication fork reversal triggers fork degradation in BRCA2-defective cells. Nature communications 313 29038466
2009 Functional restoration of BRCA2 protein by secondary BRCA2 mutations in BRCA2-mutated ovarian carcinoma. Cancer research 272 19654294
2004 Functional interaction of monoubiquitinated FANCD2 and BRCA2/FANCD1 in chromatin. Molecular and cellular biology 268 15199141
2000 Insights into the functions of BRCA1 and BRCA2. Trends in genetics : TIG 252 10652533
2007 Cancer risks among BRCA1 and BRCA2 mutation carriers. British journal of cancer 243 17213823
1998 The BRCA2 gene product functionally interacts with p53 and RAD51. Proceedings of the National Academy of Sciences of the United States of America 223 9811893
2002 Brca2 (XRCC11) deficiency results in radioresistant DNA synthesis and a higher frequency of spontaneous deletions. Molecular and cellular biology 216 11756561
2014 Cancer suppression by the chromosome custodians, BRCA1 and BRCA2. Science (New York, N.Y.) 215 24675954
2018 BRCA2 controls DNA:RNA hybrid level at DSBs by mediating RNase H2 recruitment. Nature communications 207 30560944
2006 Clinical and molecular features associated with biallelic mutations in FANCD1/BRCA2. Journal of medical genetics 197 16825431
2007 Founder mutations in BRCA1 and BRCA2 genes. Annals of oncology : official journal of the European Society for Medical Oncology 186 17591843
2007 Prostate cancer progression and survival in BRCA2 mutation carriers. Journal of the National Cancer Institute 176 17565157
2009 The contribution of BRCA1 and BRCA2 to ovarian cancer. Molecular oncology 174 19383375
2019 Genetic Screens Reveal FEN1 and APEX2 as BRCA2 Synthetic Lethal Targets. Molecular cell 170 30686591
2011 Unraveling the mechanism of BRCA2 in homologous recombination. Nature structural & molecular biology 168 21731065
2019 BRCA2 abrogation triggers innate immune responses potentiated by treatment with PARP inhibitors. Nature communications 159 31316060
2017 A Class of Environmental and Endogenous Toxins Induces BRCA2 Haploinsufficiency and Genome Instability. Cell 146 28575672
2017 BRCA2 suppresses replication stress-induced mitotic and G1 abnormalities through homologous recombination. Nature communications 137 28904335
2003 Association of biallelic BRCA2/FANCD1 mutations with spontaneous chromosomal instability and solid tumors of childhood. Blood 133 14670928
2000 Lessons learned from BRCA1 and BRCA2. Oncogene 133 11156530
2007 BRCA2: a universal recombinase regulator. Oncogene 124 18066084
2012 The role of BRCA1 and BRCA2 in prostate cancer. Asian journal of andrology 117 22522501
1996 Cell cycle control of BRCA2. Cancer research 113 8840967
2005 BRCA2 BRC motifs bind RAD51-DNA filaments. Proceedings of the National Academy of Sciences of the United States of America 110 15937124
2013 Functional assays for analysis of variants of uncertain significance in BRCA2. Human mutation 99 24323938
2007 BRCA2 is required for neurogenesis and suppression of medulloblastoma. The EMBO journal 95 17476307
2003 Direct interaction of the Fanconi anaemia protein FANCG with BRCA2/FANCD1. Human molecular genetics 85 12915460
2004 Emerging functions of BRCA2 in DNA recombination. Trends in biochemical sciences 81 15276185
1998 Functions of the BRCA1 and BRCA2 genes. Current opinion in genetics & development 81 9529600
2011 Roles of brca2 (fancd1) in oocyte nuclear architecture, gametogenesis, gonad tumors, and genome stability in zebrafish. PLoS genetics 78 21483806
2019 BRCA2 and Other DDR Genes in Prostate Cancer. Cancers 74 30871108
2013 In brief: BRCA1 and BRCA2. The Journal of pathology 73 23620175
1998 Developmental studies of Brca1 and Brca2 knock-out mice. Journal of mammary gland biology and neoplasia 71 10819537
2004 DNA recombination, chromosomal stability and carcinogenesis: insights into the role of BRCA2. DNA repair 70 15279768
2011 Brca2, Rad51 and Mre11: performing balancing acts on replication forks. DNA repair 69 21900052
2006 Histopathology of BRCA1- and BRCA2-associated breast cancer. Critical reviews in oncology/hematology 68 16530420
1997 The BRCA1 and BRCA2 breast cancer genes. Current opinion in oncology 66 9090499
2005 Regulation of BRCA1, BRCA2 and BARD1 intracellular trafficking. BioEssays : news and reviews in molecular, cellular and developmental biology 62 16108063
2018 The germline mutational landscape of BRCA1 and BRCA2 in Brazil. Scientific reports 61 29907814
2017 BRCA1 and BRCA2 tumor suppressors protect against endogenous acetaldehyde toxicity. EMBO molecular medicine 61 28729482
1997 Murine Brca2: sequence, map position, and expression pattern. Genomics 61 9119389
2018 The functional impact of variants of uncertain significance in BRCA2. Genetics in medicine : official journal of the American College of Medical Genetics 59 29988080
2016 BRCA2 functions: from DNA repair to replication fork stabilization. Endocrine-related cancer 59 27530658
2016 BRCA2 regulates DMC1-mediated recombination through the BRC repeats. Proceedings of the National Academy of Sciences of the United States of America 57 26976601
2019 The influence of BRCA2 mutation on localized prostate cancer. Nature reviews. Urology 56 30808988
2014 Rapid evolution of BRCA1 and BRCA2 in humans and other primates. BMC evolutionary biology 56 25011685
2013 Breast cancer genes: beyond BRCA1 and BRCA2. Frontiers in bioscience (Landmark edition) 56 23747889
2020 Ovarian cancer predisposition beyond BRCA1 and BRCA2 genes. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 54 32895312
2004 Chromosomal radiosensitivity in BRCA1 and BRCA2 mutation carriers. International journal of radiation biology 52 15799620
1999 BRCA1 and BRCA2 in breast cancer. Breast cancer research and treatment 52 10369075
2018 Homologous Recombination and Replication Fork Protection: BRCA2 and More! Cold Spring Harbor symposia on quantitative biology 51 29686033
2020 Proper chromosome alignment depends on BRCA2 phosphorylation by PLK1. Nature communications 48 32286328
2005 BRCA2 suppresses cell proliferation via stabilizing MAGE-D1. Cancer research 47 15930293
2017 Antimüllerian hormone levels are lower in BRCA2 mutation carriers. Fertility and sterility 46 28476184
2006 Functional assays for BRCA1 and BRCA2. The international journal of biochemistry & cell biology 45 16978908
2024 A glycolytic metabolite bypasses "two-hit" tumor suppression by BRCA2. Cell 44 38608703
2019 HSF2BP Interacts with a Conserved Domain of BRCA2 and Is Required for Mouse Spermatogenesis. Cell reports 44 31242413
2020 The BRCA2-MEILB2-BRME1 complex governs meiotic recombination and impairs the mitotic BRCA2-RAD51 function in cancer cells. Nature communications 42 32345962
2025 Functional evaluation and clinical classification of BRCA2 variants. Nature 40 39779857
2020 Molecular Trajectory of BRCA1 and BRCA2 Mutations. Frontiers in oncology 40 32269964
2001 Chromosome stability, DNA recombination and the BRCA2 tumour suppressor. Current opinion in cell biology 40 11343905
2021 Guardians of the Genome: BRCA2 and Its Partners. Genes 39 34440403
2002 BRCA2 and pancreatic cancer. International journal of gastrointestinal cancer 38 12622420
2000 Prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 38 11060335
2022 Gastric Cancer Risk and Pathogenesis in BRCA1 and BRCA2 Carriers. Cancers 36 36497436
2020 Mutations in ATM, NBN and BRCA2 predispose to aggressive prostate cancer in Poland. International journal of cancer 36 32875559
2021 A complex of BRCA2 and PP2A-B56 is required for DNA repair by homologous recombination. Nature communications 35 34593815
2017 The zebrafish kidney mutant zeppelin reveals that brca2/fancd1 is essential for pronephros development. Developmental biology 35 28579318
2011 FANCD1/BRCA2 plays predominant role in the repair of DNA damage induced by ACNU or TMZ. PloS one 35 21573016
1998 BRCA1 and BRCA2 proteins: roles in health and disease. Molecular pathology : MP 35 10193517
2019 Antagonism between BRCA2 and FIGL1 regulates homologous recombination. Nucleic acids research 34 30941419
2019 BRCA2 deficiency is a potential driver for human primary ovarian insufficiency. Cell death & disease 34 31209201
2023 Structural basis for stabilisation of the RAD51 nucleoprotein filament by BRCA2. Nature communications 33 37919288
2017 Mutations in BRCA2 and taxane resistance in prostate cancer. Scientific reports 33 28676659
2006 Functional interplay between BRCA2/FancD1 and FancC in DNA repair. The Journal of biological chemistry 33 16687415
2017 Risk of uterine cancer for BRCA1 and BRCA2 mutation carriers. European journal of cancer (Oxford, England : 1990) 32 28802188
2000 Chromosome 8p alterations in sporadic and BRCA2 999del5 linked breast cancer. Journal of medical genetics 32 10807692
1998 Expression of BRCA1 and BRCA2 in normal and neoplastic cells. Journal of mammary gland biology and neoplasia 32 10819533
2022 ZFP281-BRCA2 prevents R-loop accumulation during DNA replication. Nature communications 31 35715464
2023 BRCA2 chaperones RAD51 to single molecules of RPA-coated ssDNA. Proceedings of the National Academy of Sciences of the United States of America 30 36976771
2012 BRCA2 mutations and triple-negative breast cancer. PloS one 30 22666503
1997 Changes in BRCA2 expression during progression of the cell cycle. Biochemical and biophysical research communications 29 9168997
2020 DSS1 and ssDNA regulate oligomerization of BRCA2. Nucleic acids research 28 32609828
2009 Mutational analysis of FANCL, FANCM and the recently identified FANCI suggests that among the 13 known Fanconi Anemia genes, only FANCD1/BRCA2 plays a major role in high-risk breast cancer predisposition. Carcinogenesis 28 19737859
2008 Poly(ADP-ribose) polymerase-1 down-regulates BRCA2 expression through the BRCA2 promoter. The Journal of biological chemistry 28 18990703
2018 PALB2 (partner and localizer of BRCA2). Atlas of genetics and cytogenetics in oncology and haematology 27 31413733
2008 Secondary BRCA1 and BRCA2 alterations and acquired chemoresistance. Cancer biology & therapy 27 18720553
2022 BRCA2 gene mutation in cancer. Medicine 26 36397405
2021 Genotype-cancer association in patients with Fanconi anemia due to pathogenic variants in FANCD1 (BRCA2) or FANCN (PALB2). Cancer genetics 26 34687993
2013 BRCA1 and BRCA2 mutations and female fertility. Current opinion in obstetrics & gynecology 26 23411475

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