Direct DNA binding by Brca1
Open accessAbstract
The tumor suppressor Brca1 plays an important role in protecting mammalian cells against genomic instability, but little is known about its modes of action. In this work we demonstrate that recombinant human Brca1 protein binds strongly to DNA, an activity conferred by a domain in the center of the Brca1 polypeptide. As a result of this binding, Brca1 inhibits the nucleolytic activities of the Mre11/Rad50/Nbs1 complex, an enzyme implicated in numerous aspects of double-strand break repair. Brca1 displays a preference for branched DNA structures and forms protein-DNA complexes cooperatively between multiple DNA strands, but without DNA sequence specificity. This fundamental property of Brca1 may be an important part of its role in DNA repair and transcription.
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BRCA1 binds to Rad50 at nuclear foci and reportedly inhibits nuclease activity of the M-N-R complex.
“The breast cancer tumor suppressor protein BRCA1 binds to Rad50 at nuclear foci and reportedly inhibits nuclease activity of the M-N-R complex (7,8).”
From Mdm2 Binds to Nbs1 at Sites of DNA Damage and Regulates Double Strand Break Repair (2005) · cites this paper as [8]
Cites
Brca1 Controls Homology-Directed DNA Repair
Moynahan, M. E., Chiu, J. W., Koller, B. H., & Jasin, M. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80202-6 · Cited by 1,245 · see citing works
Wang, Y., Cortez, D., Yazdi, P., Neff, N., Elledge, S. J., & Qin, J. (2000) · Genes & Development · doi:10.1101/gad.14.8.927 · Cited by 1,221 · see citing works
Self-citationA mechanistic basis for Mre11-directed DNA joining at microhomologies
Paull, T. T., & Gellert, M. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.110144297 · Cited by 188 · see citing works
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Cancer Susceptibility and the Functions of BRCA1 and BRCA2
Venkitaraman, A. R. (2002) · Cell · doi:10.1016/s0092-8674(02)00615-3 · Cited by 1,713 · see citing works
Regulation of DNA double-strand break repair pathway choice
Shrivastav, M., De Haro, L. P., & Nickoloff, J. A. (2008) · Cell Research · doi:10.1038/cr.2007.111 · Cited by 1,329 · see citing works
Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks
Celeste, A., Fernandez-Capetillo, O., Kruhlak, M. J., Pilch, D. R., Staudt, D. W., Lee, A., Bonner, R. F., Bonner, W. M., & Nussenzweig, A. (2003) · Nature Cell Biology · doi:10.1038/ncb1004 · Cited by 989 · see citing works
Showing your ID: intrinsic disorder as an ID for recognition, regulation and cell signaling
Uversky, V. N., Oldfield, C. J., & Dunker, A. K. (2005) · Journal of Molecular Recognition · doi:10.1002/jmr.747 · Cited by 847 · see citing works
Yoshida, K., & Miki, Y. (2004) · Cancer Science · doi:10.1111/j.1349-7006.2004.tb02195.x · Cited by 753 · see citing works
Recombinational DNA repair and human disease
Thompson, L. H., & Schild, D. (2002) · Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis · doi:10.1016/s0027-5107(02)00224-5 · Cited by 417 · see citing works
BRCA1–BARD1 promotes RAD51-mediated homologous DNA pairing
Zhao, W., Steinfeld, J. B., Liang, F., Chen, X., Maranon, D. G., Jian Ma, C., Kwon, Y., Rao, T., Wang, W., Sheng, C., et al. (2017) · Nature · doi:10.1038/nature24060 · Cited by 393 · see citing works
Powell, S. N., & Kachnic, L. A. (2003) · Oncogene · doi:10.1038/sj.onc.1206678 · Cited by 364 · see citing works
Chk2 Phosphorylation of BRCA1 Regulates DNA Double-Strand Break Repair
Zhang, J., Willers, H., Feng, Z., Ghosh, J. C., Kim, S., Weaver, D. T., Chung, J. H., Powell, S. N., & Xia, F. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.2.708-718.2004 · Cited by 323 · see citing works
The role of BRCA1 in DNA damage response
Wu, J., Lu, L.-Y., & Yu, X. (2010) · Protein & Cell · doi:10.1007/s13238-010-0010-5 · Cited by 235 · see citing works
Limoli, C. L., Giedzinski, E., Bonner, W. M., & Cleaver, J. E. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.231611798 · Cited by 210 · see citing works
Dynamic alternative DNA structures in biology and disease
Wang, G., & Vasquez, K. M. (2023) · Nature Reviews Genetics · doi:10.1038/s41576-022-00539-9 · Cited by 196 · see citing works
Mdm2 Binds to Nbs1 at Sites of DNA Damage and Regulates Double Strand Break Repair
Alt, J. R., Bouska, A., Fernandez, M. R., Cerny, R. L., Xiao, H., & Eischen, C. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m413387200 · Cited by 131 · see citing works
Analysis of the DNA Substrate Specificity of the Human BACH1 HelicaseAssociated with BreastCancer
Gupta, R., Sharma, S., Sommers, J. A., Jin, Z., Cantor, S. B., & Brosh, R. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501995200 · Cited by 131 · see citing works
Distinct functions of BRCA1 and BRCA2 in double-strand break repair
Liu, Y., & West, S. C. (2001) · Breast Cancer Research · doi:10.1186/bcr417 · Cited by 87 · see citing works
Glover, J. N. M. (2006) · Familial Cancer · doi:10.1007/s10689-005-2579-z · Cited by 57 · see citing works
- Authors
- Paull, T. T., Cortez, D., Bowers, B., Elledge, S. J., & Gellert, M.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Paull, Tanya T.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2001-05-15
- Volume
- 98
- Issue
- 11
- Pages
- 6086-6091
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC33426
- OpenAlex
- W2139533668
- Cited by
- 282
- References
- 3
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 4 · 2023: 6 · 2022: 10 · 2021: 9 · 2020: 5 · 2019: 8 · 2018: 3 · 2017: 5 · 2016: 6 · 2015: 7 · 2014: 10 · 2013: 4 · 2012: 10
- FWCI
- 9.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Diffusion and Search Dynamics
- Keywords
- BRCA1, DNA binding, tumor suppressor, Mre11-Rad50-Nbs1 complex, DNA double-strand break repair, genomic instability, branched DNA, protein-DNA complex, DNA repair, transcription
- MeSH terms
- MRE11 Homologue Protein, Animals, Binding Sites, DNA, DNA Damage, DNA Repair, DNA-Binding Proteins, Exodeoxyribonucleases, Humans, Nuclear Proteins, Protein Binding, Recombinant Fusion Proteins, Genes, Tumor Suppressor, Cell Cycle Proteins, BRCA1 Protein
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