BRCA1 functions independently of homologous recombination in DNA interstrand crosslink repair
Open accessAbstract
Brca1 is required for DNA repair by homologous recombination (HR) and normal embryonic development. Here we report that deletion of the DNA damage response factor 53BP1 overcomes embryonic lethality in Brca1-nullizygous mice and rescues HR deficiency, as measured by hypersensitivity to polyADP-ribose polymerase (PARP) inhibition. However, Brca1,53BP1 double-deficient cells are hypersensitive to DNA interstrand crosslinks (ICLs), indicating that BRCA1 has an additional role in DNA crosslink repair that is distinct from HR. Disruption of the nonhomologous end-joining (NHEJ) factor, Ku, promotes DNA repair in Brca1-deficient cells; however deletion of either Ku or 53BP1 exacerbates genomic instability in cells lacking FANCD2, a mediator of the Fanconi anemia pathway for ICL repair. BRCA1 therefore has two separate roles in ICL repair that can be modulated by manipulating NHEJ, whereas FANCD2 provides a key activity that cannot be bypassed by ablation of 53BP1 or Ku.
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BRCA1 interacts with FancD2 and mediates FancD2 foci formation after mitomycin C treatment.
“Since BRCA1 interacts with FancD2 and mediates FancD2 foci formation after treatment with MMC (Bunting et al., 2012; Garcia-Higuera et al., 2001; Vandenberg et al., 2003)”
From The BRCA1-Interacting Protein Abraxas Is Required for Genomic Stability and Tumor Suppression (2014) · cites this paper as Bunting et al., 2012
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Cites
Integrated genomic analyses of ovarian carcinoma
Perou, C. M. (2019) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/hvp3-wg08 · Cited by 7,927 · see citing works
Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
Farmer, H., McCabe, N., Lord, C. J., Tutt, A. N. J., Johnson, D. A., Richardson, T. B., Santarosa, M., Dillon, K. J., Hickson, I., Knights, C., et al. (2005) · Nature · doi:10.1038/nature03445 · Cited by 6,683 · see citing works
Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase
Bryant, H. E., Schultz, N., Thomas, H. D., Parker, K. M., Flower, D., Lopez, E., Kyle, S., Meuth, M., Curtin, N. J., & Helleday, T. (2005) · Nature · doi:10.1038/nature03443 · Cited by 5,198 · see citing works
53BP1 Inhibits Homologous Recombination in Brca1-Deficient Cells by Blocking Resection of DNA Breaks
Bunting, S. F., Callén, E., Wong, N., Chen, H.-T., Polato, F., Gunn, A., Bothmer, A., Feldhahn, N., Fernandez-Capetillo, O., Cao, L., et al. (2010) · Cell · doi:10.1016/j.cell.2010.03.012 · Cited by 1,671 · see citing works
Self-citationHuman CtIP promotes DNA end resection
Sartori, A. A., Lukas, C., Coates, J., Mistrik, M., Fu, S., Bartek, J., Baer, R., Lukas, J., & Jackson, S. P. (2007) · Nature · doi:10.1038/nature06337 · Cited by 1,362 · see citing works
Self-citationInteraction of the Fanconi Anemia Proteins and BRCA1 in a Common Pathway
Garcia-Higuera, I., Taniguchi, T., Ganesan, S., Meyn, M. S., Timmers, C., Hejna, J., Grompe, M., & D'Andrea, A. D. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00173-3 · Cited by 1,198 · see citing works
Self-citationBouwman, P., Aly, A., Escandell, J. M., Pieterse, M., Bartkova, J., van der Gulden, H., Hiddingh, S., Thanasoula, M., Kulkarni, A., Yang, Q., et al. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1831 · Cited by 1,001 · see citing works
Botuyan, M. V., Lee, J., Ward, I. M., Kim, J., Thompson, J. R., Chen, J., & Mer, G. (2006) · Cell · doi:10.1016/j.cell.2006.10.043 · Cited by 973 · see citing works
Self-citationMethylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks
Huyen, Y., Zgheib, O., DiTullio Jr, R. A., Gorgoulis, V. G., Zacharatos, P., Petty, T. J., Sheston, E. A., Mellert, H. S., Stavridi, E. S., & Halazonetis, T. D. (2004) · Nature · doi:10.1038/nature03114 · Cited by 884 · see citing works
Xu, X., Ohler, Z. W., Linke, S. P., Li, C., Gotay, J., Wang, X. W., Harris, C. C., Ried, T., & Deng, C. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80466-9 · Cited by 819 · see citing works
Xu, X., Wagner, K., Larson, D. M., Ohler, Z. W., Li, C., Ried, T., Hennighausen, L. G., Wynshaw-Boris, A. J., & Deng, C. (1999) · Nature Genetics · doi:10.1038/8743 · Cited by 758 · see citing works
The MRE11 complex: starting from the ends
Stracker, T. H., & Petrini, J. H. J. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3047 · Cited by 734 · see citing works
Abraxas and RAP80 Form a BRCA1 Protein Complex Required for the DNA Damage Response
Wang, B., Matsuoka, S., Ballif, B. A., Zhang, D., Smogorzewska, A., Gygi, S. P., & Elledge, S. J. (2007) · Science · doi:10.1126/science.1139476 · Cited by 695 · see citing works
Emergence of a DNA-damage response network consisting of Fanconi anaemia and BRCA proteins
Wang, W. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2159 · Cited by 663 · see citing works
Requirement for Ku80 in growth and immunoglobulin V(D)J recombination
Nussenzweig, A., Chen, C., Soares, V. D. C., Sanchez, M., Sokol, K. A., Nussenzweig, M. C., & Li, G. C. (1996) · Nature · doi:10.1038/382551a0 · Cited by 662 · see citing works
Self-citationKu80: product of the XRCC5 gene and its role in DNA repair and V(D)J recombination
Taccioli, G. E., Gottlieb, T. M., Blunt, T., Priestley, A., Demengeot, J., Mizuta, R., Lehmann, A. R., Alt, F. W., Jackson, S. P., & Jeggo, P. A. (1994) · Science · doi:10.1126/science.8073286 · Cited by 638 · see citing works
DNA end-joining: from yeast to man
Critchlow, S. E., & Jackson, S. P. (1998) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(98)01284-5 · Cited by 584 · see citing works
Bhattacharyya, A., Ear, U., Koller, B. H., Weichselbaum, R. R., & Bishop, D. K. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.c000276200 · Cited by 584 · see citing works
53BP1 promotes non-homologous end joining of telomeres by increasing chromatin mobility
Dimitrova, N., Chen, Y.-C. M., Spector, D. L., & de Lange, T. (2008) · Nature · doi:10.1038/nature07433 · Cited by 572 · see citing works
DNA helicases Sgs1 and BLM promote DNA double-strand break resectionPreprint
Gravel, S., Chapman, J. R., Magill, C. P., & Jackson, S. P. (2008) · Genes & Development · doi:10.1101/gad.503108 · Cited by 562 · see citing works
CtIP-BRCA1 modulates the choice of DNA double-strand-break repair pathway throughout the cell cycle
Yun, M. H., & Hiom, K. (2009) · Nature · doi:10.1038/nature07955 · Cited by 556 · see citing works
Increased ratio of targeted to random integration after transfection of chicken B cell lines
Buerstedde, J.-M., & Takeda, S. (1991) · Cell · doi:10.1016/0092-8674(91)90581-i · Cited by 543 · see citing works
Patel, A. G., Sarkaria, J. N., & Kaufmann, S. H. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1013715108 · Cited by 543 · see citing works
Ludwig, T. E., Chapman, D. L., Papaioannou, V. E., & Efstratiadis, A. (1997) · Genes & Development · doi:10.1101/gad.11.10.1226 · Cited by 539 · see citing works
Self-citationThe Fanconi Anemia Pathway Promotes Replication-Dependent DNA Interstrand Cross-Link Repair
Knipscheer, P., Räschle, M., Smogorzewska, A., Enoiu, M., Ho, T. V., Schärer, O. D., Elledge, S. J., & Walter, J. C. (2009) · Science · doi:10.1126/science.1182372 · Cited by 515 · see citing works
Ku DNA end-binding protein modulates homologous repair of double-strand breaks in mammalian cellsPreprint
Pierce, A. J., Hu, P., Han, M., Ellis, N. A., & Jasin, M. (2001) · Genes & Development · doi:10.1101/gad.946401 · Cited by 514 · see citing works
BRCA1 tumour suppression occurs via heterochromatin-mediated silencing
Zhu, Q., Pao, G. M., Huynh, A. M., Suh, H., Tonnu, N. U., Nederlof, P. M., Gage, F. H., & Verma, I. M. (2011) · Nature · doi:10.1038/nature10371 · Cited by 486 · see citing works
BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA damage
Yarden, R. I., Pardo-Reoyo, S., Sgagias, M. K., Cowan, K. H., & Brody, L. C. (2002) · Nature Genetics · doi:10.1038/ng837 · Cited by 483 · see citing works
p53 Binding Protein 53BP1 Is Required for DNA Damage Responses and Tumor Suppression in Mice
Ward, I. M., Minn, K. T., van Deursen, J., & Chen, J. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.7.2556-2563.2003 · Cited by 412 · see citing works
DNA resection in eukaryotes: deciding how to fix the break
Huertas, P. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1710 · Cited by 398 · see citing works
Xu, X., Qiao, W., Linke, S. P., Cao, L., Li, W., Furth, P. A., Harris, C. C., & Deng, C. (2001) · Nature Genetics · doi:10.1038/90108 · Cited by 372 · see citing works
53BP1 links DNA damage-response pathways to immunoglobulin heavy chain class-switch recombination
Manis, J. P., Morales, J. C., Xia, Z., Kutok, J. L., Alt, F. W., & Carpenter, P. B. (2004) · Nature Immunology · doi:10.1038/ni1067 · Cited by 337 · see citing works
Collaboration and competition between DNA double‐strand break repair pathways
Kass, E. M., & Jasin, M. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.07.057 · Cited by 326 · see citing works
Origin of Chromosomal Translocations in Lymphoid Cancer
Nussenzweig, A., & Nussenzweig, M. C. (2010) · Cell · doi:10.1016/j.cell.2010.03.016 · Cited by 315 · see citing works
Self-citationExpanded roles of the Fanconi anemia pathway in preserving genomic stabilityPreprint
Kee, Y., & D’Andrea, A. D. (2010) · Genes & Development · doi:10.1101/gad.1955310 · Cited by 309 · see citing works
Self-citationCao, L., Xu, X., Bunting, S. F., Liu, J., Wang, R.-H., Cao, L. L., Wu, J. J., Peng, T.-N., Chen, J., Nussenzweig, A., et al. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.06.037 · Cited by 308 · see citing works
Self-citation53BP1 facilitates long-range DNA end-joining during V(D)J recombination
Difilippantonio, S., Gapud, E. J., Wong, N., Huang, C., Mahowald, G. K., Chen, H. T., Kruhlak, M. J., Callén, E., Livák, F., Nussenzweig, M. C., et al. (2008) · Nature · doi:10.1038/nature07476 · Cited by 302 · see citing works
Self-citationPreventing Nonhomologous End Joining Suppresses DNA Repair Defects of Fanconi Anemia
Adamo, A., Collis, S. J., Adelman, C. A., Silva, N., Hořejšı́, Z., Ward, J. D., Martínez-Pérez, E., Boulton, S. J., & Volpe, A. L. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.06.026 · Cited by 297 · see citing works
Yamane, A., Resch, W., Kuo, N., Kuchen, S., Li, Z., Sun, H., Robbiani, D. F., McBride, K. M., Nussenzweig, M. C., & Casellas, R. C. (2010) · Nature Immunology · doi:10.1038/ni.1964 · Cited by 289 · see citing works
Bothmer, A., Robbiani, D. F., Feldhahn, N., Gazumyan, A., Nussenzweig, A., & Nussenzweig, M. C. (2010) · The Journal of Experimental Medicine · doi:10.1084/jem.20100244 · Cited by 283 · see citing works
Self-citationEpithelial cancer in Fanconi anemia complementation group D2 (Fancd2) knockout micePreprint
Houghtaling, S. R., Timmers, C. D., Noll, M., Finegold, M. J., Jones, S. N., Meyn, M. S., & Grompe, M. (2003) · Genes & Development · doi:10.1101/gad.1103403 · Cited by 262 · see citing works
Regulation of DNA End Joining, Resection, and Immunoglobulin Class Switch Recombination by 53BP1
Bothmer, A., Robbiani, D. F., Di Virgilio, M., Bunting, S. F., Klein, I. A., Feldhahn, N., Barlow, J., Chen, H.-T., Bosque, D., Callen, E., et al. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.03.019 · Cited by 244 · see citing works
Self-citationKu70 Corrupts DNA Repair in the Absence of the Fanconi Anemia Pathway
Pace, P., Mosedale, G., Hodskinson, M. R. G., Rosado, I. V., Sivasubramaniam, M., & Patel, K. J. (2010) · Science · doi:10.1126/science.1192277 · Cited by 239 · see citing works
Mechanism of RAD51-Dependent DNA Interstrand Cross-Link Repair
Long, D. T., Räschle, M., Joukov, V., & Walter, J. C. (2011) · Science · doi:10.1126/science.1204258 · Cited by 238 · see citing works
Absence of a Ku-like DNA end binding activity in the xrs double-strand DNA repair-deficient mutant.
Getts, R. C., & Stamato, T. D. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)33960-1 · Cited by 237 · see citing works
Ye, Q., Hu, Y.-F., Zhong, H.-J., Nye, A. C., Belmont, A. S., & Li, R. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.200108049 · Cited by 204 · see citing works
ATM Prevents the Persistence and Propagation of Chromosome Breaks in Lymphocytes
Callén, E., Janković, M., Difilippantonio, S., Daniel, J. A., Chen, H. T., Celeste, A., Pellegrini, M., McBride, K. M., Wangsa, D., Bredemeyer, A. L., et al. (2007) · Cell · doi:10.1016/j.cell.2007.06.016 · Cited by 178 · see citing works
Self-citationA DNA End-Binding Factor Involved in Double-Strand Break Repair and V(D)J Recombination
Rathmell, W. K., & Chu, G. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.7.4741 · Cited by 166 · see citing works
BRCA1-independent ubiquitination of FANCD2
Vandenberg, C. J., Gergely, F., Ong, C. Y., Pace, P., Mallery, D. L., Hiom, K., & Patel, K. J. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00281-8 · Cited by 131 · see citing works
Integrated genomic analyses of ovarian carcinoma
The Cancer Genome Atlas Research Network (2011) · Nature · doi:10.1038/nature10166 · Cited by 129 · see citing works
Fancd2 −/− mice have hematopoietic defects that can be partially corrected by resveratrol
Zhang, Q., Loza, L. I. M., Eaton, L., Duncan, A. W., Goldman, D. C., Anur, P., Watanabe‐Smith, K., Rathbun, R. K., Fleming, W., Bagby, G. C., et al. (2010) · Blood · doi:10.1182/blood-2010-04-278226 · Cited by 106 · see citing works
Jensen, R. B., & Glazer, P. M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400051101 · Cited by 89 · see citing works
The Fanconi anemia pathway: Repairing the link between DNA damage and squamous cell carcinoma
Romick‐Rosendale, L. E., Lui, V. W. Y., Grandis, J. R., & Wells, S. I. (2013) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2013.01.001 · Cited by 65 · see citing works
Houghtaling, S. R., Newell, A. H., Akkari, Y. M. N., Taniguchi, T., Olson, S. B., & Grompe, M. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi334 · Cited by 57 · see citing works
A DNA End-Binding Factor Involved in Double-Strand Break Repair and V(D)J Recombination
Rathmell, W. K., & Chu, G. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.7.4741-4748.1994 · Cited by 44 · see citing works
Other Options in the Treatment of Advanced Breast Cancer
Cobleigh, M. (2011) · Seminars in Oncology · doi:10.1053/j.seminoncol.2011.04.005 · Cited by 31 · see citing works
A new nuclease member of the FAN club
Huang, M., & D'Andrea, A. D. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb0810-926 · Cited by 29 · see citing works
Self-citationCloning and Characterization of Rat Ku70: Involvement of Ku Autoantigen in the Heat-Shock Response
Yang, S.-H., Nussenzweig, A., Wei-hong, Y., et al. (1996) · Radiation Research · doi:10.2307/3579375 · Cited by 16 · see citing works
Self-citationBRCA1: A locus‐specific “liaison” in gene expression and genetic integrity
Aiyar, S. E., Sun, J., & Li, R. (2005) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20386 · Cited by 6 · see citing works
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Johnson, S. F., Cruz, C., Greifenberg, A. K., Dust, S., Stover, D. G., Chi, D., Primack, B., Cao, S., Bernhardy, A. J., Coulson, R., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.10.077 · Cited by 291 · see citing works
Self-citationBouwman, P., van der Gulden, H., van der Heijden, I., Drost, R., Klijn, C. N., Prasetyanti, P., Pieterse, M., Wientjens, E., Seibler, J., Hogervorst, F. B. L., et al. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0094 · Cited by 140 · see citing works
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- Authors
- Bunting, S. F., Callén, E., Kozak, M. L., Kim, J. M., Wong, N., López-Contreras, A. J., Ludwig, T., Baer, R., Faryabi, R. B., Malhowski, A., Chen, H.-T., Fernandez-Capetillo, O., D'Andrea, A., & Nussenzweig, A.
- Affiliations
- National Institutes of Health (US)
- Harvard University (US)
- Columbia University Irving Medical Center (US)
- Corresponding author
- Nussenzweig, André
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2012-04
- Volume
- 46
- Issue
- 2
- Pages
- 125-135
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC3340543
- OpenAlex
- W2047119008
- Cited by
- 252
- References
- 59
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 5 · 2023: 9 · 2022: 6 · 2021: 24 · 2020: 20 · 2019: 18 · 2018: 21 · 2017: 19 · 2016: 30 · 2015: 16 · 2014: 28 · 2013: 33 · 2012: 20
- FWCI
- 12.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- Funders
- National Institutes of Health (Z99 CA999999)
- U.S. Bureau of Land Management
- National Heart, Lung, and Blood Institute (R37HL052725)
- National Cancer Institute (K99 CA160574, Y99 CA999999, Z01BC010283, 1K99CA160574-01, Z01BC010959)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK043889)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Keywords
- BRCA1, interstrand crosslink repair, homologous recombination, 53BP1, Ku, non-homologous end joining, FANCD2, Fanconi anemia pathway, genomic instability, embryonic lethality, DNA damage response
- MeSH terms
- Ku Autoantigen, Animals, DNA Repair, DNA-Binding Proteins, Sequence Deletion, BRCA1 Protein, Antigens, Nuclear, Genomic Instability, Mice, Fanconi Anemia Complementation Group D2 Protein, Gene Knockdown Techniques, Homologous Recombination
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