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Cited by 393DNA Repair MechanismsBRCA gene mutations in cancerPARP inhibition in cancer therapy

BRCA1–BARD1 promotes RAD51-mediated homologous DNA pairing

Open access
Zhao, Weixing, Steinfeld, Justin B., Liang, Fengshan, Chen, Xiaoyong, Maranon, David G., Jian Ma, Chu, Kwon, Youngho, Rao, Timsi +12 more·2017·Nature
DOI 10.1038/nature24060PMC PMC5800781
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Abstract

The tumour suppressor complex BRCA1-BARD1 functions in the repair of DNA double-stranded breaks by homologous recombination. During this process, BRCA1-BARD1 facilitates the nucleolytic resection of DNA ends to generate a single-stranded template for the recruitment of another tumour suppressor complex, BRCA2-PALB2, and the recombinase RAD51. Here, by examining purified wild-type and mutant BRCA1-BARD1, we show that both BRCA1 and BARD1 bind DNA and interact with RAD51, and that BRCA1-BARD1 enhances the recombinase activity of RAD51. Mechanistically, BRCA1-BARD1 promotes the assembly of the synaptic complex, an essential intermediate in RAD51-mediated DNA joint formation. We provide evidence that BRCA1 and BARD1 are indispensable for RAD51 stimulation. Notably, BRCA1-BARD1 mutants with weakened RAD51 interactions show compromised DNA joint formation and impaired mediation of homologous recombination and DNA repair in cells. Our results identify a late role of BRCA1-BARD1 in homologous recombination, an attribute of the tumour suppressor complex that could be targeted in cancer therapy.

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Registry

Crossref · 10.1038/nature24060

Cites

55 of 55 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 18 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    BRCA1-BARD1 binds 4-5 RAD51 molecules.

    “We also determined that 4–5 RAD51 molecules are bound by BRCA1-BARD1”
    Quote in the paperSubstantial claim
  • Findingown data

    Unlike BRCA2-DSS1, BRCA1-BARD1 fails to promote assembly of RAD51 presynaptic filaments on RPA-coated ssDNA.

    “while, as reported previously36,38, the BRCA2-DSS1 complex promotes RAD51 presynaptic filament assembly on RPA-coated ssDNA, BRCA1-BARD1 does not possess such an attribute”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [36] Zhao, W. et al. Promotion of BRCA2-dependent homologous recombination by DSS1 via RPA targeting and DNA mimicry. Mol. Cell 59, 176–187 (2015) source

      Not checked in the free run.

    • cites [38] Jensen, R. B., Carreira, A. & Kowalczykowski, S. C. Purified human BRCA2 stimulates RAD51-mediated recombination. Nature 467, 678–683 (2010) source

      Not checked in the free run.

  • Findingown data

    The RAD51 interaction domain in BRCA1-BARD1 was identified.

    “Extended Data Fig. 6 Identification of the RAD51 interaction domain in BRCA1-BARD1”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The antibodies used in immunoblotting are specific for their intended targets.
  • Findingown data

    When both BARD1 and 53BP1 are absent, the AAE mutant complements the HR defect less well than wild-type BARD1.

    “In cells lacking both BARD1 and 53BP1, BARD1AAEres was less capable than BARD1WTres in complementing the HR deficiency (Extended Data Fig. 8l, m).”
    Quote in the paperSubstantial claim
  • Findingown data

    BARD1 truncation mutants vary in their ability to interact with RAD51.

    “Summary of the RAD51 interaction ability of BARD1 truncation mutants, based on the pulldown analyses in e (for BRCA1-BARD1, BRCA11-500-BARD1 and BRCA11-500-BARD11-261), f (for BRCA11-500-BARD1, BRCA11-500-BARD11-261 and BRCA11-500-BARD11-122), g (for BRCA11-500-BARD1Δ123-261, BRCA11-500-BARD1Δ123-162, BRCA11-500-BARD11-261 and BRCA11-500-BARD11-162) and h (for BARD1123-162).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The antibodies used in immunoblotting are specific for their intended targets.
  • May combine two claims. 30
  • Classified as probably not a substantial claim. 10
  • The quote only partly states this claim. 2

  • May combine two claims.

    Findingown data

    The complex binds human RAD51, while showing little or no binding to yeast Rad51 or E. coli RecA.

    “we found that BRCA1-BARD1 interacts with human RAD51 but has little or no affinity for yeast Rad51 (yRad51) (Fig. 1d) or E. coli RecA”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    BRCA1 and BARD1 each bind the D-loop, and BARD1 appears to bind it more strongly.

    “we found that both BRCA1 and BARD1 bind the D-loop, with BARD1 showing an apparently higher affinity for the substrate”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The BRCA1-BARD1 complex binds DNA, preferring the D-loop and DNA bubble most, then the replication fork, dsDNA, and ssDNA.

    “The results revealed that BRCA1-BARD1 has the highest affinity for the D-loop and DNA bubble, followed by the RF, dsDNA, and ssDNA”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In Far Western assays, BRCA1 and BARD1 each retained RAD51, and BARD1 gave the stronger signal.

    “both BRCA1 and BARD1 retained RAD51 in the Far Western assay, with BARD1 showing a more robust signal”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Benzonase and ethidium bromide do not disrupt assembly of the BRCA1-BARD1-RAD51 complex.

    “formation of the BRCA1-BARD1-RAD51 complex was not affected by benzonase or ethidium bromide”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    When dsDNA is present, BRCA1-BARD1 cannot target RAD51 to ssDNA, whereas BRCA2-DSS1 can.

    “unlike BRCA2-DSS137,38, BRCA1-BARD1 is devoid of the ability to target RAD51 to ssDNA when dsDNA is present”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [37] San Filippo, J. et al. Recombination mediator and Rad51 targeting activities of a human BRCA2 polypeptide. J. Biol. Chem. 281, 11649–11657 (2006) source

      Not checked in the free run.

    • cites [38] Jensen, R. B., Carreira, A. & Kowalczykowski, S. C. Purified human BRCA2 stimulates RAD51-mediated recombination. Nature 467, 678–683 (2010) source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    In BARD1-deficient cells, wild-type BARD1 fully rescues HR, whereas the AAE mutant only partly does.

    “while the ectopic expression of BARD1WTres in BARD1 deficient cells fully restored HR proficiency, that of BARD1AAEres resulted in only partial complementation”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Ectopically expressed Flag-SBP tagged wild type and mutant BARD1 were less abundant than endogenous BARD1.

    “As the abundance of ectopically expressed Flag-SBP tagged wild type and mutant BARD1 was lower than endogenous BARD1, we revealed it with anti-Flag antibody in Western blot analysis.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The antibodies used in immunoblotting are specific for their intended targets.

  • May combine two claims.

    Findingown data

    Under two conditions-pre-incubating ssDNA with RAD51, or premixing ssDNA and plasmid DNA-BRCA2-DSS1 did not stimulate D-loop formation by BRCA1-BARD1-RAD51.

    “We found no stimulatory effect of BRCA2-DSS1 on D-loop formation by BRCA1-BARD1-RAD51 when the ssDNA substrate was pre-incubated with RAD51 or when ssDNA and plasmid DNA were premixed”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The complex does not alter where bound dsDNA sits, the distances between bound molecules, or their koff.

    “we found no evidence of BRCA1-BARD1 having any effect on the binding site distributions, the pairwise distance distributions, and the resident time (koff) of the bound dsDNA”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    A GST-tagged BARD1 piece containing residues 123-162 binds RAD51, so this segment contains the interaction domain.

    “a GST-tagged BARD1 fragment harboring these residues could efficiently associate with RAD51 (Extended Data Fig. 6h), indicating that it encompasses the RAD51 interaction domain”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Depleting BRCA1 reduces RAD51 focus formation, both spontaneously and after γ-rays.

    “knockdown of endogenous BRCA1 diminished RAD51 focus formation, either spontaneously or after γ-ray exposure”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    By RPA32 S4/S8 phosphorylation, AAE cells show more persistent DNA damage 72 h after MMC release.

    “as indicated by S4/S8 phosphorylation of RPA32, BARD1AAEres cells retained a much higher level of DNA damage 72 h after release from MMC treatment”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    RAD51's core domain, T3, binds BRCA1-BARD1, but not the BRCA1-BARD11-142 or BRCA11-500-BARD1 complexes.

    “the core domain of RAD51 (referred to as T3), which has been implicated in BRCA2 binding via the BRC4 repeat of the latter41, is able to interact with BRCA1-BARD1 (Extended Data Fig. 3f), but not with BRCA1-BARD11-142 or BRCA11-500-BARD1”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [41] Pellegrini, L. et al. Insights into DNA recombination from the structure of a RAD51–BRCA2 complex. Nature 420, 287–293 (2002) source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Mutants defective in BARD1-RAD51 binding, or missing BRCA1's RAD51 interaction domain, cannot promote pairing with the duplex target.

    “BRCA1-BARD1 mutants impaired for BARD1-RAD51 interaction or lacking the RAD51 interaction domain of BRCA1 are unable to promote pairing with the duplex target”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The Δ123-162 mutant binds DNA normally yet cannot bind RAD51 and does not boost D-loop or synaptic complex assembly.

    “We found that BRCA1-BARD1Δ123-162, while retaining normal DNA binding activity (Extended Data Fig. 7a, b), is defective in RAD51 interaction (Fig. 4c) and, accordingly, fails to enhance D-loop formation (Fig. 4d, e) or synaptic complex assembly (Extended Data Fig. 7c, d).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Substoichiometric BRCA1-BARD1 strongly boosts D-loop formation with either ATP or AMP-PNP, but BRCA2-DSS1 does not.

    “Importantly, BRCA1-BARD1, in amounts substoichiometric to RAD51, strongly enhanced the reaction, regardless of whether ATP (Extended Data Fig. 4g–i) or the non-hydrolyzable analogue AMP-PNP (Fig. 2a–c) was used as the nucleotide cofactor, while BRCA2-DSS1 did not show any stimulation”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    BARD1 K140N, a cancer-associated change, leaves DNA binding intact but weakens RAD51 binding and the complex's ability to promote D-loop and synaptic complex assembly.

    “Importantly, the results revealed that, while the mutation has no impact on DNA binding (Extended Data Fig. 7a, b), it attenuates the affinity of BRCA1-BARD1 for RAD51 (Fig. 4c) and also compromises the ability of the tumor suppressor complex to enhance D-loop formation and synaptic complex assembly (Fig. 4d, e and Extended Data Fig. 7c, d).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    BRCA1 and BARD1 play a role in homologous recombination and RAD51 focus formation.

    “Extended Data Fig. 8 Role of BRCA1 and BARD1 in HR and RAD51 focus formation”
    Quote in the paperSubstantial claim
    • Rests on an assumption: RAD51 focus formation is a valid marker of homologous recombination.
    • Rests on an assumption: The DR-GFP reporter assay measures homologous recombination proficiency.

  • May combine two claims.

    Findingown data

    siRNA depletion of BRCA1 or BARD1 lowers HR in both the DR-GFP and CRISPR/Cas9 gene-targeting assays.

    “knockdown of endogenous BRCA1 or BARD1 by siRNA impaired HR in both systems”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The AAE mutant binds DNA normally, but its RAD51 binding and its ability to stimulate D-loop and synaptic complex assembly are reduced.

    “Biochemical testing revealed that, even though the mutant complex binds DNA normally (Extended Data Fig. 7a, b), it is impaired not only for RAD51 association (Fig. 4c), but also for the ability to stimulate D-loop formation and synaptic complex assembly (Fig. 4d, e; Extended Data Figs. 5g and 7c, d).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Loss of 53BP1 partly rescues the HR defect from BRCA1 deficiency, but not the defect in BARD1-deficient cells.

    “Interestingly, even though depletion of 53BP1, an inhibitor of DNA end resection50, partially overcame the HR defect associated with BRCA1 deficiency (Extended Data Fig. 8h, i), it did not suppress the HR defect in BARD1 deficient cells (Extended Data Fig. 8j, k).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [50] Bunting, S. F. et al. 53BP1 inhibits homologous recombination in brca1-deficient cells by blocking resection of DNA breaks. Cell 141, 243–254 (2010) source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    The BRCA11-500-BARD1 and BRCA1Δ758-1064-BARD1 mutants bind DNA well but bind RAD51 weakly, and neither strongly promotes RAD51 D-loop or synaptic complex assembly.

    “These mutant complexes appeared to be proficient in DNA binding (Extended Data Fig. 10a–e) but were weakened for RAD51 interaction (Extended Data Fig. 10f–h). Importantly, neither mutant complex could strongly enhance RAD51-mediated D-loop formation (Extended Data Fig. 10i, j) or synaptic complex assembly (Extended Data Figs. 5g and 7c–f).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The complex's RAD51 binding is species-specific, and both BRCA1 and BARD1 take part in it.

    “These results helped establish that BRCA1-BARD1 associates with RAD51 in a species-specific manner, and that both proteins in the complex participate in RAD51 interaction.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Each protein, BRCA1 and BARD1, adds to the complex's ability to bind DNA.

    “Taken together, our results showed that both BRCA1 and BARD1 contribute to the DNA binding capability of the BRCA1-BARD1 complex.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The threshold for detecting RAD51 foci was set using sham-irradiated samples.

    “The threshold for foci detection was determined based on sham-irradiated samples”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The DR-GFP assay results came from 3 to 5 transfections across at least 3 independent experiments.

    “The results were derived from 3 to 5 transfections of at least 3 independent experiments.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Unless otherwise stated, statistical significance was assessed with a two-tailed unpaired Student's t-test.

    “Unless stated otherwise, statistical significance was assessed by two-tailed unpaired Student’s t-test.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    BARD1 K140N, a cancer-associated mutation, weakens both physical and functional interaction with RAD51.

    “we have provided evidence that the cancer-associated mutation K140N in BARD1 compromises the physical and functional interactions of BRCA1-BARD1 with RAD51”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    P values of 0.05 or less and 0.01 or less were considered significant.

    “P ≤ 0.05 (*) and P≤ 0.01 (**) was considered significant.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    RAD51 binding probably helps the presynaptic filament engage dsDNA, and BRCA1-BARD1's recognition of unwound DNA likely promotes the nascent DNA joint in the D-loop.

    “It is likely that physical association with RAD51 facilitates dsDNA engagement by the presynaptic filament and that the specific recognition of unwound DNA by BRCA1-BARD1 enhances the formation of the nascent DNA joint in the D-loop reaction.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    The DR-U2OS cell line used in the study carries one integrated copy of the DR-GFP reporter.

    “The DR-U2OS cell line containing a single integrated copy of the DR-GFP reporter was used46,47.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [46] Nakanishi, K. et al. Human Fanconi anemia monoubiquitination pathway promotes homologous DNA repair. Proc. Natl Acad. Sci. USA 102, 1110–1115 (2005) source

      Not checked in the free run.

    • cites [47] Xia, B. et al. Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2. Mol. Cell 22, 719–729 (2006) source

      Not checked in the free run.

    • Rests on an assumption: The DR-GFP reporter assay measures homologous recombination proficiency.

  • May combine two claims.

    Interpretationown data

    AAE cells are defective in HR repair despite normal RAD51 focus formation.

    “These results showed that HR repair is deficient in BARD1AAEres cells even though RAD51 focus formation is not affected.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    BRCA1-BARD1 works with the RAD51 presynaptic filament to build the synaptic complex, which precedes D-loop formation.

    “Mechanistically, BRCA1-BARD1 functions with the RAD51 presynaptic filament in the assembly of the synaptic complex, a critical precursor to D-loop formation”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Group allocation and outcome assessment in the RAD51 foci experiments were fully blinded.

    “Group allocation and outcome assessment were done in a fully blinded manner.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Statistical analysis used Prism 7 on data from at least three independent experiments.

    “The statistical analysis was performed using Prism 7 (GraphPad Software, Inc., La Jolla, CA; http://www.graphpad.com/quickcalcs/ttest1.cfm) on the data from at least three independent experiments, as specified.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premiseown data

    The complex aids resection of DNA ends, producing a single-stranded template that recruits BRCA2-PALB2 and RAD51.

    “BRCA1-BARD1 facilitates the nucleolytic resection of DNA ends to generate a single-stranded template for the recruitment of another tumor suppressor complex BRCA2-PALB2 and the recombinase RAD51.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [4] Prakash, R., Zhang, Y., Feng, W. & Jasin, M. Homologous recombination and human health: the roles of BRCA1, BRCA2, and associated proteins. Cold Spring Harb. Perspect. Biol. 7, a016600 (2015) source

      Not checked in the free run.

    • cites [33] Daley, J. M. & Sung, P. 53BP1, BRCA1, and the choice between recombination and end joining at DNA double-strand breaks. Mol. Cell. Biol. 34, 1380–1388 (2014) source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The nuclear localization of endogenous BRCA1 and ectopically expressed Flag-SBP tagged BARD1 or the AAE mutant in HeLa cells was verified by Western blot.

    “Western blot to verify the nuclear localization of endogenous BRCA1 and ectopically expressed Flag-SBP tagged BARD1 or the AAE mutant in HeLa cells.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The antibodies used in immunoblotting are specific for their intended targets.

  • Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

    Study design and conductown data

    The CRISPR/Cas9 gene targeting assay results came from 3 to 5 transfections across at least 3 independent experiments.

    “The results were derived from 3 to 5 transfections of at least 3 independent experiments.”
    Quote in the paperNot a substantial claim
39 of 39

  • The paper relies on this without support.

    RAD51 focus formation is a valid marker of homologous recombination.

    “Quantification of RAD51 foci at various time points after exposure to 4 Gy γ-rays or sham irradiation.”

  • The paper relies on this without support.

    The DR-GFP reporter assay measures homologous recombination proficiency.

    “HR proficiency was determined by counting the fraction of GFP-positive cells using a BD FACS Calibur S at 72 h post I-SceI transfection.”

  • The paper relies on this without support.

    The antibodies used in immunoblotting are specific for their intended targets.

    “Blots (20–50 μg of total protein) were probed with the following antibodies: BARD1 (Bethyl, A300-263A; Santa Cruz Biotech, Sc11438), BRCA1 (Abcam, ab16780), 53BP1 (Abcam, ab36823), Flag M2-HRP (Sigma, A8592), Phospho RPA32 S4/S8 (Bethyl, A300-245A), BRCA2 (EMD Millipore, OP95-100UG), RAD51 (Santa Cruz Biotech, sc-8349), Actin (Abcam, ab3280), Tubulin (Santa Cruz Biotech, sc-53030), HA.11 (16B12) (”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The 4 patients with deficiencies in BRCA1-binding proteins BARD1, BRIP1, FAM175A and FANCA were all predicted as having BRCA1-type HRD.

    “Likewise, the 4 patients with deficiencies in the BRCA1-binding proteins, BARD124 (n = 1), BRIP125 (n = 1), FAM175A26 (n = 1) and FANCA27 (n = 1), were all predicted as having BRCA1-type HRD.”

    From Pan-cancer landscape of homologous recombination deficiency. (2020) · cites this paper as [24]

Cites

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Related

Authors
Zhao, W., Steinfeld, J. B., Liang, F., Chen, X., Maranon, D. G., Jian Ma, C., Kwon, Y., Rao, T., Wang, W., Sheng, C., Song, X., Deng, Y., Jimenez-Sainz, J., Lu, L., Jensen, R. B., Xiong, Y., Kupfer, G. M., Wiese, C., Greene, E. C., & Sung, P.
Affiliations
  • Yale University (US)
  • Columbia University (US)
  • Colorado State University (US)
Corresponding author
  • Zhao, Weixing
  • Greene, Eric C.
  • Sung, Patrick
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2017-10
Volume
550
Issue
7676
Pages
360-365
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature24060
PMC
PMC5800781
OpenAlex
W2763077107
Cited by
393
References
56
Citations by year
2026: 41 · 2025: 38 · 2024: 42 · 2023: 50 · 2022: 44 · 2021: 56 · 2020: 61 · 2019: 36 · 2018: 22 · 2017: 2 · 2012: 1
FWCI
13.45
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • University of Pennsylvania Health System
  • Abramson Cancer Center
  • National Institutes of Health (UL1TR001863)
  • National Cancer Institute (F31CA210663, R01CA215990, R01CA220123, R01CA168635, P01CA092584)
  • National Institute of General Medical Sciences (R35GM118026)
  • National Institute of Environmental Health Sciences (R01ES021454, R56ES021454, R01ES007061)
  • National Center for Advancing Translational Sciences
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
  • Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
Keywords
RAD51, homologous recombination, DNA double-strand break repair, synaptic complex, BRCA1, BARD1, single-stranded DNA, hereditary breast cancer, cancer therapy targets
MeSH terms
Fanconi Anemia Complementation Group N Protein, Amino Acid Sequence, Humans, Mutation, Protein Binding, Sequence Homology, Nucleic Acid, Templates, Genetic, BRCA1 Protein, Genes, BRCA1, Base Pairing, Chromosome Pairing, Genes, BRCA2, BRCA2 Protein, Tumor Suppressor Proteins, Ubiquitin-Protein Ligases, Multiprotein Complexes, Rad51 Recombinase, Recombinational DNA Repair

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