Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response

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 w...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1999-07, Vol.285 (5428), p.747-750
Main Authors: QING ZHONG, CHEN, C.-F, SHANG LI, YUMAY CHEN, WANG, C.-C, JUN XIAO, CHEN, P.-L, SHARP, Z. D, LEE, W.-H
Format: Article
Language:English
Subjects:
Acid Anhydride Hydrolases
Biological and medical sciences
BRCA1 Protein - metabolism
Breast cancer
Cell Cycle Proteins - metabolism
Cell Nucleus - metabolism
Cell physiology
Cell Survival
Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
Cells
Deoxyribonucleic acid
DNA
DNA Damage
DNA Repair Enzymes
DNA-Binding Proteins - metabolism
Fundamental and applied biological sciences. Psychology
Gamma Rays
Genes
Genes, BRCA1
Humans
Methyl Methanesulfonate - pharmacology
Molecular and cellular biology
MRE11 Homologue Protein
Mutagens - pharmacology
Mutation
Nuclear Proteins
Proteins
Rad51 Recombinase
Radiation
Recombination, Genetic
Transfection
Tumor Cells, Cultured
Tumors
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.285.5428.747