Affinage

BRCA1

Breast cancer type 1 susceptibility protein · UniProt P38398

Length
1863 aa
Mass
207.7 kDa
Annotated
2026-06-09
100 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BRCA1 is a multifunctional nuclear tumor suppressor that safeguards genome integrity by promoting error-free homologous recombination (HR) repair of DNA double-strand breaks and limiting mutagenic nonhomologous repair (PMID:10549283). It executes HR through two genetically separable activities: a coiled-coil-dependent function that counteracts the 53BP1-RIF1-Shieldin axis to license DNA end resection, and a Δ11-region/PALB2-dependent function that loads RAD51 onto resected DNA, with RNF168 acting redundantly with BRCA1 in the PALB2-loading step (PMID:30704900, PMID:32359443). BRCA1 functions as a RING-domain heterodimer with BARD1; cryo-EM of the BRCA1-BARD1–nucleosome complex shows BARD1 ankyrin and BRCT domains reading nucleosomal histones, DNA, and the DSB-specific H2A K13/K15 monoubiquitin mark while the RING domains position an E2 enzyme for C-terminal H2A ubiquitylation that opposes 53BP1 (PMID:34321665). Recruitment to ionizing-radiation-induced foci requires cooperation of the BRCA1 RING and BRCT domains and co-localization with MDC1, with cancer mutations abolishing targeting (PMID:15569676), and BRCA1 retention at breaks is organized by the RAP80/Abraxas(CCDC98)/MERIT40-containing BRCA1-A complex, which controls foci formation and the G2/M checkpoint (PMID:17643121, PMID:19261748). Heterodimer assembly and DNA-damage localization are tuned by SIRT2-mediated deacetylation of the BARD1 RING interface, while BAP1 antagonizes the BRCA1/BARD1 ligase through both catalytic and non-catalytic mechanisms (PMID:33789098, PMID:19117993). As an E3 ubiquitin ligase BRCA1/BARD1 modifies substrates including topoisomerase IIα, regulating DNA decatenation and chromosome segregation (PMID:15965487), and estrogen receptor-α, repressing its transcriptional activity (PMID:19887647). BRCA1 activity is integrated into genotoxic stress signaling through ATR phosphorylation of multiple residues including Ser1423 at stalled replication forks (PMID:11114888) and through p53/CRM1-dependent nuclear export after DNA damage (PMID:15087457). Beyond repair, BRCA1 maintains centromere stability by resolving R-loops at α-satellite repeats to preserve CENP-A loading (PMID:34599155), supports XIST RNA concentration and chromatin structure on the inactive X chromosome (PMID:12419249), and acts as a transcriptional regulator—autorepressing its own promoter via a BRCA1/E2F1/Rb complex dissolved by genotoxic stress (PMID:20068145) and controlling target genes such as SIRT1 and the ferroptosis regulators VDAC3 and GPX4 (PMID:18851829, PMID:38552003).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1999 High

    Established BRCA1's foundational caretaker role by showing it is required for accurate double-strand break repair rather than acting indirectly, defining the genome-stability function that frames all later mechanism.

    Evidence Brca1 knockout mouse embryonic stem cells with DSB repair frequency assays

    PMID:10549283

    Open questions at the time
    • Did not identify the molecular partners executing HR
    • Did not separate resection from RAD51-loading roles
  2. 2000 High

    Placed BRCA1 downstream of replication-stress and damage signaling by identifying ATR as a kinase that phosphorylates it at defined residues, linking BRCA1 localization to the genotoxic checkpoint machinery.

    Evidence In vitro kinase assay, dominant-negative kinase-inactive ATR, foci co-localization at stalled forks

    PMID:11114888

    Open questions at the time
    • Functional consequence of each phosphosite not fully resolved
    • Relationship to ATM-dependent sites not addressed here
  3. 2002 High

    Extended BRCA1 function beyond break repair to chromatin maintenance, showing it associates with XIST RNA and is needed for inactive-X chromatin integrity.

    Evidence ChIP, immunofluorescence, BRCA1 reconstitution, silenced GFP reporter on Xi

    PMID:12419249

    Open questions at the time
    • Direct vs. indirect role in XIST localization unresolved
    • Mechanism connecting BRCA1 to XIST concentration unknown
  4. 2003 High

    Clarified the in vivo relevance of BRCA1/BARD1 E3 ligase activity by demonstrating that, despite reconstituting FANCD2 monoubiquitination in vitro, the ligase is dispensable for that modification in cells, tightening claims about its physiological substrates.

    Evidence In vitro ubiquitination reconstitution, siRNA knockdown, RING ablation in DT40 cells

    PMID:12887909

    Open questions at the time
    • The bona fide essential in vivo substrates of BRCA1/BARD1 left undefined
    • How BRCA1 affects FANCD2 accumulation at damage sites without ubiquitinating it unclear
  5. 2004 Medium

    Defined the domain logic of BRCA1 recruitment, showing RING and BRCT domains must cooperate for foci targeting and that cancer mutations disrupt this, linking genotype to localization failure.

    Evidence YFP-tagged domain mapping, live-cell imaging after IR, MDC1 co-localization

    PMID:15569676

    Open questions at the time
    • Direct ligand bound by the cooperating domains not defined here
    • Single lab, imaging-based
  6. 2004 Medium

    Identified topoisomerase IIα as a BRCA1-dependent ubiquitination target and connected BRCA1 to chromosome segregation through DNA decatenation, broadening its mechanistic repertoire beyond HR.

    Evidence Co-IP, co-localization, in vitro decatenation assay, ubiquitination assay in BRCA1-deficient cells

    PMID:15965487

    Open questions at the time
    • Ubiquitin chain type and lysine sites on TopoIIα not mapped
    • Single lab
  7. 2004 Medium

    Revealed a damage-responsive layer of BRCA1 regulation by showing p53- and CRM1-dependent nuclear export after IR, adding spatial control to its activity.

    Evidence Subcellular fractionation, leptomycin B, HPV E6 p53 inactivation, inducible p53 system

    PMID:15087457

    Open questions at the time
    • Functional purpose of damage-induced export unresolved
    • Export signal within BRCA1 not mapped
  8. 2007 Medium

    Built the BRCA1-A complex by identifying Abraxas/CCDC98 as the adaptor linking BRCA1 to RAP80, explaining how BRCA1 foci form and how the G2/M checkpoint is enforced.

    Evidence Reciprocal Co-IP, siRNA knockdown, foci analysis, checkpoint assay

    PMID:17643121

    Open questions at the time
    • Stoichiometry and full subunit architecture not resolved here
    • Single lab
  9. 2008 Medium

    Established BRCA1 as a sequence-specific transcriptional activator beyond its own locus, showing it drives SIRT1 expression to suppress Survivin via histone modification.

    Evidence ChIP, promoter reporter, siRNA epistasis, mouse tumor model

    PMID:18851829

    Open questions at the time
    • Direct DNA-binding vs. cofactor recruitment at SIRT1 promoter unresolved
    • Single lab
  10. 2009 High

    Defined antagonistic and assembly regulation of the ligase: BAP1 inhibits BRCA1/BARD1 ubiquitination by both catalytic and non-catalytic means, and MERIT40 stabilizes the five-subunit BRCA1-A complex at breaks.

    Evidence Co-IP, surface plasmon resonance, in vitro ubiquitination with C91S mutant, foci and checkpoint assays

    PMID:19117993 PMID:19261748

    Open questions at the time
    • In vivo significance of BAP1 inhibition for tumor suppression not established here
    • MERIT40 dependence in other BRCA1 complexes unaddressed
  11. 2009 Medium

    Connected BRCA1 ligase activity to hormone signaling by showing it monoubiquitinates and represses estrogen receptor-α, with a ligase-dead I26A mutant losing this function.

    Evidence In vitro ubiquitination and acetylation assays, I26A and C61G mutants, siRNA knockdown

    PMID:19887647

    Open questions at the time
    • In vivo contribution to estrogen-driven tumorigenesis not measured here
    • Single lab
  12. 2010 Medium

    Defined an autoregulatory transcriptional loop: BRCA1 represses its own promoter in a BRCA1/E2F1/Rb complex that is disassembled by genotoxic stress to upregulate BRCA1.

    Evidence Tandem/sequential ChIP, promoter reporter, BRCA1 knockdown and overexpression

    PMID:20068145

    Open questions at the time
    • Signal that dissolves the complex not identified
    • Single lab
  13. 2020 High

    Resolved how a single protein executes two opposing HR steps by demonstrating RNF168 redundancy with BRCA1 in PALB2 loading and defining separation-of-function alleles for resection (coiled-coil) versus RAD51 loading (Δ11).

    Evidence Compound mutant and double/triple knockout mouse genetics, RAD51 foci, PARP inhibitor sensitivity, forced PALB2 targeting

    PMID:30704900 PMID:32359443

    Open questions at the time
    • Molecular basis of coiled-coil counteraction of Shieldin not structurally defined
    • How RNF168 substitutes for BRCA1 at the PALB2 step mechanistically unresolved
  14. 2021 High

    Provided the structural mechanism of BRCA1/BARD1 nucleosome recognition and ubiquitin transfer, explaining how the heterodimer reads the H2A K13/K15 DSB mark and writes C-terminal H2A ubiquitin to oppose 53BP1.

    Evidence Cryo-EM of BRCA1-BARD1–nucleosome complex, in vitro ubiquitylation, structure-guided mutagenesis

    PMID:34321665

    Open questions at the time
    • Structural basis for substrate selectivity among other BRCA1 targets not addressed
    • How this activity integrates with full BRCA1-A complex unresolved
  15. 2021 Medium

    Identified upstream regulation of heterodimer assembly via SIRT2 deacetylation of the BARD1 RING interface and extended BRCA1 function to centromere protection through R-loop resolution at α-satellite repeats.

    Evidence Co-IP and deacetylation assays with SIRT2 depletion (HR/foci readouts); ChIP, DRIP, micronuclei scoring and Rad52 epistasis for centromeres

    PMID:33789098 PMID:34599155

    Open questions at the time
    • Whether SIRT2 regulation operates in vivo during tumorigenesis unknown
    • Mechanism by which BRCA1 resolves centromeric R-loops not defined
  16. 2024 Medium

    Linked BRCA1 transcriptional control to ferroptosis vulnerability, showing it activates VDAC3 and GPX4 and that BRCA1 deficiency creates a GPX4-inhibitor and PARPi synergy via NCOA4-mediated ferritinophagy.

    Evidence Reporter assays, ChIP, viability assays with GPX4i/PARPi, NCOA4 knockdown, xenografts

    PMID:38552003

    Open questions at the time
    • Direct vs. indirect transcriptional control of VDAC3/GPX4 not fully resolved
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How BRCA1's many activities—HR, transcription, ubiquitin ligation toward diverse substrates, R-loop resolution, and chromatin maintenance—are coordinated within distinct complexes and which are most critical for tumor suppression remains unresolved.
  • No unified model linking ligase activity to HR in vivo
  • Relative tumor-suppressive weight of transcriptional vs. repair functions undefined
  • Substrate selectivity rules for BRCA1/BARD1 unmapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 5 GO:0003677 DNA binding 3 GO:0140096 catalytic activity, acting on a protein 3 GO:0140110 transcription regulator activity 3 GO:0140098 catalytic activity, acting on RNA 1
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3 GO:0005654 nucleoplasm 2
Pathway
R-HSA-73894 DNA Repair 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1640170 Cell Cycle 3 R-HSA-4839726 Chromatin organization 3 R-HSA-8953897 Cellular responses to stimuli 2
Partners
ATRBAP1BARD1CCDC98MERIT40PALB2RAP80SIRT2
Complex memberships
BRCA1-A complex (RAP80/Abraxas/MERIT40/BRCC45)BRCA1-BARD1 heterodimerBRCA1/E2F1/Rb repressive complex

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Brca1-deficient mouse embryonic stem cells have impaired repair of chromosomal DNA double-strand breaks (DSBs) by homologous recombination, with altered relative frequencies of homologous vs. nonhomologous DNA integration and DSB repair, demonstrating a caretaker role for BRCA1 in promoting homologous recombination and limiting mutagenic nonhomologous repair. Genetic knockout in mouse embryonic stem cells with DSB repair frequency assays Molecular cell High 10549283
2000 ATR phosphorylates BRCA1 on six Ser/Thr residues including Ser1423 in vitro and in vivo in response to UV light, hydroxyurea, aphidicolin, and partially in response to ionizing radiation. ATR and BRCA1 co-localize in nuclear foci at stalled replication forks, placing them in the same genotoxic stress-responsive pathway. In vitro kinase assay, kinase-inactive ATR dominant-negative expression, immunofluorescence co-localization of nuclear foci Genes & development High 11114888
2002 BRCA1 colocalizes with markers of the inactive X chromosome (Xi) in female somatic cells and physically associates with XIST RNA as detected by chromatin immunoprecipitation. BRCA1-deficient cells show defects in Xi chromatin structure and XIST RNA concentration; reconstitution of BRCA1-deficient cells with wild-type BRCA1 restored focal XIST RNA staining and reduced re-expression of a silenced Xi-located GFP transgene. Chromatin immunoprecipitation, immunofluorescence, BRCA1 reconstitution in deficient cells, GFP reporter assay Cell High 12419249
2003 The purified BRCA1/BARD1 complex, together with E1 and UbcH5a, is sufficient to reconstitute monoubiquitination of FANCD2 in vitro. However, siRNA-mediated knockdown of BRCA1 in human cells does not lead to a defect in FANCD2 ubiquitination, and ablation of RING finger domains of BRCA1 or BARD1 in DT40 cells leaves FANCD2 modification intact. BRCA1 affects accumulation of FANCD2 at DNA damage sites but BRCA1/BARD1 E3 ligase activity is not essential for FANCD2 monoubiquitination in vivo. In vitro ubiquitination reconstitution, siRNA knockdown, RING domain ablation in DT40 cells Molecular cell High 12887909
2003 BRCA1 interacts with processive (hyperphosphorylated, IIO form) RNA polymerase II rather than the hypophosphorylated promoter-associated form (IIA) in undamaged cells. BRCA1-RNA pol II complexes are highly functional in transcriptional run-off assays and the interaction is disrupted by DNA-damaging agents. Fractionation, co-immunoprecipitation, transcriptional run-off assay The Journal of biological chemistry Medium 14506230
2004 BRCA1 interacts and colocalizes with topoisomerase IIα in S-phase cells. BRCA1-deficient cells show lagging chromosomes and defective DNA decatenation in vitro, phenocopying topoisomerase IIα inhibition. Topoisomerase IIα is ubiquitinated in a BRCA1-dependent manner, and its ubiquitination correlates with higher DNA decatenation activity. Co-immunoprecipitation, co-localization, in vitro decatenation assay, ubiquitination assay in BRCA1-deficient cells Nature structural & molecular biology Medium 15965487
2004 BRCA1 RING and BRCT domains cooperate to target BRCA1 to ionizing radiation-induced nuclear foci. Cancer mutations in the BRCT domain abolish recruitment. A RING-BRCT fusion restores foci targeting, co-localizes with MDC1, and inhibits entry of endogenous BRCA1 into foci. Neither RING nor BRCT domain alone is sufficient for targeting. YFP-tagged domain mapping, live-cell fluorescence imaging, ionizing radiation treatment, co-localization with MDC1 The Journal of biological chemistry Medium 15569676
2007 CCDC98 (Abraxas) is a component of the BRCA1-RAP80 complex that mediates BRCA1's association with RAP80, controls DNA damage-induced formation of BRCA1 foci, and is required for BRCA1-dependent G2/M checkpoint activation. Co-immunoprecipitation, siRNA knockdown, immunofluorescence foci analysis, checkpoint assay Nature structural & molecular biology Medium 17643121
2008 BRCA1 binds the SIRT1 promoter and increases SIRT1 expression, which in turn inhibits Survivin by altering epigenetic modification of histone H3. Absence of SIRT1 blocks BRCA1's regulation of Survivin. Chromatin immunoprecipitation, promoter reporter assay, siRNA knockdown, Western blot, mouse tumor model Molecular cell Medium 18851829
2009 BRCA1-associated protein 1 (BAP1) interacts with the RING finger domain of BARD1 and interferes with the BRCA1/BARD1 E3 ligase association via surface plasmon resonance. BAP1 inhibits BRCA1 autoubiquitination and NPM1/B23 ubiquitination by BRCA1/BARD1. A catalytically inactive BAP1 mutant (C91S) still inhibits ubiquitination, indicating a second non-catalytic inhibitory mechanism. Co-immunoprecipitation, BIAcore surface plasmon resonance, in vitro ubiquitination assay, catalytically inactive mutant (C91S), shRNA knockdown Cancer research High 19117993
2009 MERIT40 (a 40 kDa protein) assembles into the RAP80/CCDC98-containing BRCA1-A complex via direct interaction with BRE/BRCC45, and is required for maintaining stability of BRE and the five-subunit complex at DNA damage sites, thereby regulating BRCA1 retention at DNA breaks and checkpoint function. Co-immunoprecipitation, siRNA knockdown, immunofluorescence foci analysis, checkpoint assay Genes & development Medium 19261748
2009 BRCA1 overexpression reduces acetylation of estrogen receptor-α (ER-α) and increases mono-ubiquitination of ER-α; a BRCA1 mutant defective for ubiquitin ligase activity (I26A) failed to ubiquitinate ER-α or repress its transcriptional activity in vivo. Wild-type BRCA1 but not cancer mutant C61G inhibited p300-mediated acetylation of ER-α in vitro. In vitro ubiquitination assay, in vitro acetylation assay, siRNA knockdown, overexpression of BRCA1 ubiquitin-ligase-dead mutant (I26A), Western blot Molecular endocrinology Medium 19887647
2010 BRCA1 assembles with complexes containing E2F-1 and RB to form a repressive multicomponent transcriptional complex that inhibits BRCA1 promoter transcription (autoregulatory loop). Genotoxic stress disrupts this complex, displacing BRCA1 from its own promoter and upregulating BRCA1 transcription. Tandem ChIP confirmed the BRCA1/E2F1/Rb complex at the BRCA1 promoter in vivo. Chromatin immunoprecipitation (sequential/tandem ChIP), promoter-reporter assay, BRCA1 knockdown and overexpression Cancer research Medium 20068145
2019 RNF168 acts redundantly with BRCA1 to load PALB2 onto damaged DNA. Loss of RNF168 negates synthetic rescue of BRCA1 deficiency by 53BP1 deletion. Forced targeting of PALB2 to DNA breaks circumvents BRCA1 haploinsufficiency. BRCA1 promotes two distinct steps of homologous recombination: DNA end resection (counteracting 53BP1) and RAD51 loading (via PALB2 recruitment). Genetic epistasis (double and triple KO mice), RAD51 foci assay, PARP inhibitor sensitivity, forced PALB2 targeting Molecular cell High 30704900
2020 BRCA1 promotes two genetically separable activities in homologous recombination: (1) counteracting 53BP1-RIF1-Shieldin to promote DNA end resection (via the coiled-coil domain) and (2) promoting RAD51 loading (via the Δ11 region). Brca1CC and Brca1Δ11 alleles are separation-of-function mutations that complement each other to provide sufficient HR for normal development. Mouse genetics (Brca1CC/Δ11 compound heterozygotes), HR assays, RAD51 foci, 53BP1-RIF1 epistasis Molecular cell High 32359443
2021 Cryo-EM structure of BRCA1-BARD1 bound to nucleosome revealed that ankyrin repeat and tandem BRCT domains in BARD1 bind nucleosomal histones, DNA, and monoubiquitin on H2A K13/K15 (DSB-specific marks). RING domains in BRCA1-BARD1 orient an E2 ubiquitin-conjugating enzyme atop the nucleosome for ubiquitin transfer to flexible C-terminal tails of H2A/H2AX. Recognition of N-terminal H2A monoubiquitin blocks polyubiquitin chain formation and cooperatively promotes C-terminal H2A ubiquitylation, opposing 53BP1. Cryo-electron microscopy, biochemical ubiquitylation assays, structure-guided mutational analysis Nature High 34321665
2021 SIRT2 deacetylase complexes with BRCA1-BARD1 and deacetylates conserved lysines in the BARD1 RING domain at the BRCA1-BARD1 interface, promoting BRCA1-BARD1 heterodimerization, mutual stability, nuclear retention, localization to DNA damage sites, and efficient homologous recombination. Co-immunoprecipitation, deacetylation assay, SIRT2 knockdown/knockout, HR assay, immunofluorescence foci analysis Cell reports Medium 33789098
2021 BRCA1 associates with centromeric chromatin in an R-loop-dependent manner and counteracts accumulation of R-loops at centromeric α-satellite repeats. BRCA1-deficient cells show impaired CENP-A localization, increased centromeric RNA transcription, increased centromeric breakage, acentric micronuclei, and Rad52-dependent hyper-recombination at centromeric satellites, all R-loop-dependent. Chromatin immunoprecipitation, immunofluorescence, BRCA1 knockdown, R-loop detection (DRIP), micronuclei scoring, Rad52 epistasis Cell death & disease Medium 34599155
1999 Casein kinase 2 (CK2) β-subunit associates with the carboxy-terminal region of BRCA1 (yeast two-hybrid and Sf9 cell confirmation) and phosphorylates BRCA1 in vitro at Ser1572; the cancer-associated missense mutation M1775R in BRCA1 weakens the CK2β association. Yeast two-hybrid, in vitro kinase assay, site-directed mutagenesis Biochemical and biophysical research communications Low 10403822
2000 BRCA1 physically associates with ATF1 (a CREB/ATF transcription factor) via the BRCA1 RING finger domain in vitro, in yeast, and in human cells. BRCA1 stimulates transcription from a CRE reporter gene and from the TNF-α promoter in a CRE-dependent manner. Yeast two-hybrid, co-immunoprecipitation, in vitro binding, transient transfection reporter assay The Journal of biological chemistry Low 10945975
2004 DNA damage (ionizing radiation) induces BRCA1 nuclear export in a dose-dependent, CRM1-dependent manner that also requires wild-type p53 function. BRCA1 nuclear export occurs across all cell cycle phases, representing a p53-dependent regulatory mechanism of BRCA1 localization in response to DNA damage. Immunohistochemical staining, subcellular fractionation and Western blot, CRM1 inhibitor (leptomycin B), p53 inactivation by HPV E6, tetracycline-inducible p53 system The Journal of biological chemistry Medium 15087457
2024 BRCA1 promotes transcription of both VDAC3 and GPX4; BRCA1 deficiency blocks VDAC3-dependent erastin-induced ferroptosis but sensitizes cells to GPX4 inhibitor-induced ferroptosis. NCOA4-mediated ferritinophagy and defective GPX4 induction synergize PARPi and GPX4 inhibition to induce ferroptosis in BRCA1-deficient cancer cells. Transcriptional reporter assay, ChIP, cell viability assays with GPX4i and PARPi, NCOA4 knockdown, xenograft models Cancer discovery Medium 38552003

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
2021 Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer. The New England journal of medicine 1266 34081848
1999 Brca1 controls homology-directed DNA repair. Molecular cell 1021 10549283
2004 BRCA1 and BRCA2: 1994 and beyond. Nature reviews. Cancer 692 15343273
2000 Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress. Genes & development 410 11114888
2009 BRCA1 and its toolbox for the maintenance of genome integrity. Nature reviews. Molecular cell biology 401 20029420
2008 Interplay among BRCA1, SIRT1, and Survivin during BRCA1-associated tumorigenesis. Molecular cell 289 18851829
2003 BRCA1 expression modulates chemosensitivity of BRCA1-defective HCC1937 human breast cancer cells. British journal of cancer 283 12698198
2000 Roles of BRCA1 and its interacting proteins. BioEssays : news and reviews in molecular, cellular and developmental biology 257 10918303
2000 Insights into the functions of BRCA1 and BRCA2. Trends in genetics : TIG 252 10652533
2002 BRCA1 supports XIST RNA concentration on the inactive X chromosome. Cell 230 12419249
2014 Cancer suppression by the chromosome custodians, BRCA1 and BRCA2. Science (New York, N.Y.) 215 24675954
2003 BRCA1 gene in breast cancer. Journal of cellular physiology 208 12767038
1995 Mutation analysis of the BRCA1 gene in ovarian cancers. Cancer research 205 7606717
2009 BRCA1-associated protein 1 interferes with BRCA1/BARD1 RING heterodimer activity. Cancer research 180 19117993
2009 The contribution of BRCA1 and BRCA2 to ovarian cancer. Molecular oncology 174 19383375
2010 The role of BRCA1 in DNA damage response. Protein & cell 173 21203981
2014 Effects of BRCA1- and BRCA2-related mutations on ovarian and breast cancer survival: a meta-analysis. Clinical cancer research : an official journal of the American Association for Cancer Research 156 25348513
2020 BAP1: Not just a BRCA1-associated protein. Cancer treatment reviews 144 32877777
2016 RANKL/RANK control Brca1 mutation- . Cell research 139 27241552
1997 Complex regulation of the BRCA1 gene. The Journal of biological chemistry 134 9261099
2000 Lessons learned from BRCA1 and BRCA2. Oncogene 133 11156530
2009 MERIT40 facilitates BRCA1 localization and DNA damage repair. Genes & development 132 19261748
2007 CCDC98 targets BRCA1 to DNA damage sites. Nature structural & molecular biology 129 17643121
2015 A BRCA1-interacting lncRNA regulates homologous recombination. EMBO reports 128 26412854
2009 BRCA1 regulates acetylation and ubiquitination of estrogen receptor-alpha. Molecular endocrinology (Baltimore, Md.) 123 19887647
2012 Mechanisms of BRCA1 tumor suppression. Cancer discovery 114 22843421
2021 Mechanisms of BRCA1-BARD1 nucleosome recognition and ubiquitylation. Nature 113 34321665
2003 BRCA1-independent ubiquitination of FANCD2. Molecular cell 112 12887909
2003 Emerging roles of BRCA1 alternative splicing. Molecular pathology : MP 112 12890739
2006 Is there more to BARD1 than BRCA1? Nature reviews. Cancer 99 16633366
2002 Roles of BRCA1 in centrosome duplication. Oncogene 99 12214252
2019 BRCA1 Haploinsufficiency Is Masked by RNF168-Mediated Chromatin Ubiquitylation. Molecular cell 96 30704900
2005 BRCA1 participates in DNA decatenation. Nature structural & molecular biology 95 15965487
2012 Links between genome integrity and BRCA1 tumor suppression. Trends in biochemical sciences 91 22836122
2000 Estrogens, BRCA1, and breast cancer. Cancer research 86 11016617
2016 Targeting BRCA1- and BRCA2-deficient cells with RAD52 small molecule inhibitors. Nucleic acids research 84 26873923
2005 BRCA1 regulation of transcription. Cancer letters 82 15975711
2020 Comprehensive molecular comparison of BRCA1 hypermethylated and BRCA1 mutated triple negative breast cancers. Nature communications 81 32719340
2017 BRCA1 gene: function and deficiency. International journal of clinical oncology 77 28884397
2014 Role of BRCA1 in brain development. Proceedings of the National Academy of Sciences of the United States of America 76 24639535
2013 In brief: BRCA1 and BRCA2. The Journal of pathology 73 23620175
2015 Deciphering the BRCA1 Tumor Suppressor Network. The Journal of biological chemistry 72 26048987
2000 BRCA1 and cell signaling. Oncogene 71 11156529
2006 Histopathology of BRCA1- and BRCA2-associated breast cancer. Critical reviews in oncology/hematology 68 16530420
2005 BRCA1 in hormonal carcinogenesis: basic and clinical research. Endocrine-related cancer 65 16172191
2003 BRCA1 associates with processive RNA polymerase II. The Journal of biological chemistry 63 14506230
2005 Regulation of BRCA1, BRCA2 and BARD1 intracellular trafficking. BioEssays : news and reviews in molecular, cellular and developmental biology 62 16108063
1999 Emerging roles of BRCA1 in transcriptional regulation and DNA repair. Journal of cellular physiology 62 10528224
2010 Transcriptional autoregulation by BRCA1. Cancer research 59 20068145
2004 DNA damage induces p53-dependent BRCA1 nuclear export. The Journal of biological chemistry 59 15087457
1999 BRCA1 mutations in African Americans. Human genetics 57 10480351
1999 Regulation of BRCA1 by protein degradation. Oncogene 57 10597248
2004 The BRCA1 RING and BRCT domains cooperate in targeting BRCA1 to ionizing radiation-induced nuclear foci. The Journal of biological chemistry 56 15569676
2003 Breast cancer gene 1 (BRCA1): role in cell cycle regulation and DNA repair--perhaps through transcription. Journal of cellular biochemistry 56 12647291
2000 BRCA1 physically and functionally interacts with ATF1. The Journal of biological chemistry 56 10945975
1994 The search for BRCA1. Cancer research 56 7987831
2009 The complex relationship between BRCA1 and ERalpha in hereditary breast cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 55 19223511
1999 Is TP53 dysfunction required for BRCA1-associated carcinogenesis? Molecular and cellular endocrinology 55 10580847
2003 BRCA1 in cancer, cell cycle and genomic stability. Frontiers in bioscience : a journal and virtual library 53 12957814
1999 BRCA1 and BRCA2 in breast cancer. Breast cancer research and treatment 52 10369075
2013 BRCA1 in the DNA damage response and at telomeres. Frontiers in genetics 51 23802008
2019 Synergistic lethality between BRCA1 and H3K9me2 loss reflects satellite derepression. Genes & development 48 30804228
1999 The functions of breast cancer susceptibility gene 1 (BRCA1) product and its associated proteins. Biological chemistry 48 10195418
2014 BRCA1 and Oxidative Stress. Cancers 47 24704793
1999 Positive regulation of the BRCA1 promoter. The Journal of biological chemistry 47 10085126
1996 Mutations of the BRCA1 gene in human cancer. Seminars in cancer biology 46 8695765
2006 Functional assays for BRCA1 and BRCA2. The international journal of biochemistry & cell biology 45 16978908
2024 BRCA1-Mediated Dual Regulation of Ferroptosis Exposes a Vulnerability to GPX4 and PARP Co-Inhibition in BRCA1-Deficient Cancers. Cancer discovery 44 38552003
2020 BRCA1 Mutational Complementation Induces Synthetic Viability. Molecular cell 44 32359443
2015 BRCA1 Mutation: A Predictive Marker for Radiation Therapy? International journal of radiation oncology, biology, physics 44 26383678
2023 Preneoplastic stromal cells promote BRCA1-mediated breast tumorigenesis. Nature genetics 43 36914836
2021 BRCA1 prevents R-loop-associated centromeric instability. Cell death & disease 43 34599155
2021 The BRCA1/BARD1 ubiquitin ligase and its substrates. The Biochemical journal 42 34591954
2019 Moving Mountains-The BRCA1 Promotion of DNA Resection. Frontiers in molecular biosciences 41 31552267
2003 BRCA1 and p53: compensatory roles in DNA repair. Journal of molecular medicine (Berlin, Germany) 41 13679996
2013 BRCA1- and BRCA2-related mutations: therapeutic implications in ovarian cancer. Annals of oncology : official journal of the European Society for Medical Oncology 39 24131965
2010 BRCA1 16 years later: risk-associated BRCA1 mutations and their functional implications. The FEBS journal 39 20608970
2006 BRCA1 phosphorylation: biological consequences. Cancer biology & therapy 39 16721040
1999 Casein kinase 2 binds to and phosphorylates BRCA1. Biochemical and biophysical research communications 39 10403822
2001 BRCA1 and prostate cancer. Cancer investigation 38 11405179
2018 Decapping protein EDC4 regulates DNA repair and phenocopies BRCA1. Nature communications 36 29511213
2016 Factors forming the BRCA1-A complex orchestrate BRCA1 recruitment to the sites of DNA damage. Acta biochimica et biophysica Sinica 36 27325824
2014 A portable BRCA1-HAC (human artificial chromosome) module for analysis of BRCA1 tumor suppressor function. Nucleic acids research 36 25260588
2006 Assessing the link between BACH1 and BRCA1 in the FA pathway. Cell cycle (Georgetown, Tex.) 36 16357529
2006 BRCA1-mediated ubiquitylation. Cell cycle (Georgetown, Tex.) 36 16861894
2010 BRCA1 16 years later: DNA damage-induced BRCA1 shuttling. The FEBS journal 35 20608971
2001 Human BRCA1 gene rescues the embryonic lethality of Brca1 mutant mice. Genesis (New York, N.Y. : 2000) 35 11170347
1998 BRCA1: a review of structure and putative functions. Disease markers 35 9553742
2009 Aromatase expression is increased in BRCA1 mutation carriers. BMC cancer 34 19445691
2021 SIRT2 promotes BRCA1-BARD1 heterodimerization through deacetylation. Cell reports 33 33789098
2017 Out-RANKing BRCA1 in Mutation Carriers. Cancer research 33 28104682
2013 TNRC9 downregulates BRCA1 expression and promotes breast cancer aggressiveness. Cancer research 32 23447579
2007 p53, BRCA1 and breast Cancer chemoresistance. Advances in experimental medicine and biology 32 17993233
2002 Transactivation of repair genes by BRCA1. Cancer biology & therapy 32 12496474
2004 Association of BRCA1 with the inactive X chromosome and XIST RNA. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 31 15065664
2023 Long-molecule scars of backup DNA repair in BRCA1- and BRCA2-deficient cancers. Nature 30 37587346
2004 Understanding germ-line mutations in BRCA1. Cancer biology & therapy 30 15254424
2022 BRCA1: An Endocrine and Metabolic Regulator. Frontiers in endocrinology 29 35432218
2004 BRCA1 and transcription. Cancer biology & therapy 29 15254397

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