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Science 30 July 1999:
Vol. 285. no. 5428, pp. 747 - 750
DOI: 10.1126/science.285.5428.747
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Reports

Association of BRCA1 with the hRad50-hMre11-p95 Complex and the DNA Damage Response

Qing Zhong, Chi-Fen Chen, Shang Li, Yumay Chen, Chuan-Cheng Wang, Jun Xiao, Phang-Lang Chen, Z. Dave Sharp, Wen-Hwa Lee *

BRCA1 encodes a tumor suppressor that is mutated in familial breast and ovarian cancers. Here, it is shown that BRCA1 interacts in vitro and in vivo with hRad50, which forms a complex with hMre11 and p95/nibrin. Upon irradiation, BRCA1 was detected in discrete foci in the nucleus, which colocalize with hRad50. Formation of irradiation-induced foci positive for BRCA1, hRad50, hMre11, or p95 was dramatically reduced in HCC/1937 breast cancer cells carrying a homozygous mutation in BRCA1 but was restored by transfection of wild-type BRCA1. Ectopic expression of wild-type, but not mutated, BRCA1 in these cells rendered them less sensitive to the DNA damage agent, methyl methanesulfonate. These data suggest that BRCA1 is important for the cellular responses to DNA damage that are mediated by the hRad50-hMre11-p95 complex.

Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245, USA.
*   To whom correspondence should be addressed. E-mail: leew{at}uthscsa.edu

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Reconstitution of the mammalian DNA double-strand break end-joining reaction reveals a requirement for an Mre11/Rad50/NBS1-containing fraction.
J. Huang and W. S. Dynan (2002)
Nucleic Acids Res. 30, 667-674
   Abstract »    Full Text »    PDF »
A DNA Damage-Regulated BRCT-Containing Protein, TopBP1, Is Required for Cell Survival.
K. Yamane, X. Wu, and J. Chen (2002)
Mol. Cell. Biol. 22, 555-566
   Abstract »    Full Text »    PDF »
BRCA1-induced large-scale chromatin unfolding and allele-specific effects of cancer-predisposing mutations.
Q. Ye, Y.-F. Hu, H. Zhong, A. C. Nye, A. S. Belmont, and R. Li (2001)
J. Cell Biol. 155, 911-922
   Abstract »    Full Text »    PDF »
Identification of a {gamma}-Tubulin-binding Domain in BRCA1.
L.-C. Hsu, T. P. Doan, and R. L. White (2001)
Cancer Res. 61, 7713-7718
   Abstract »    Full Text »    PDF »
Redistribution of BRCA1 among Four Different Protein Complexes following Replication Blockage.
N. Chiba and J. D. Parvin (2001)
J. Biol. Chem. 276, 38549-38554
   Abstract »    Full Text »    PDF »
Fanconi anemia and DNA repair.
M. Grompe and A. D'Andrea (2001)
Hum. Mol. Genet. 10, 2253-2259
   Abstract »    Full Text »    PDF »
BRCA1 mediates ligand-independent transcriptional repression of the estrogen receptor.
L. Zheng, L. A. Annab, C. A. Afshari, W.-H. Lee, and T. G. Boyer (2001)
PNAS
   Abstract »    Full Text »    PDF »
Impaired DNA Damage Response in Cells Expressing an Exon 11-Deleted Murine Brca1 Variant That Localizes to Nuclear Foci.
L. J. Huber, T. W. Yang, C. J. Sarkisian, S. R. Master, C.-X. Deng, and L. A. Chodosh (2001)
Mol. Cell. Biol. 21, 4005-4015
   Abstract »    Full Text »
Selected Features of Nonendocrine Pancreatic Cancer.
K. M. Anderson and J. E. Harris (2001)
Experimental Biology and Medicine 226, 521-537
   Abstract »    Full Text »    PDF »
Homology-directed DNA Repair, Mitomycin-C Resistance, and Chromosome Stability Is Restored with Correction of a Brca1 Mutation.
M. E. Moynahan, T. Y. Cui, and M. Jasin (2001)
Cancer Res. 61, 4842-4850
   Abstract »    Full Text »    PDF »
BRCA1 at a branch point.
J. D. Parvin (2001)
PNAS 98, 5952-5954
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