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

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Abstract

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, BRCR1 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.

Original languageEnglish (US)
Pages (from-to)747-750
Number of pages4
JournalScience
Volume285
Issue number5428
DOIs
Publication statusPublished - Jul 30 1999

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ASJC Scopus subject areas

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Cite this

Zhong, Q., Chen, C. F., Li, S., Chen, Y., Wang, C. C., Xiao, J., ... Lee, W. H. (1999). Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response. Science, 285(5428), 747-750. https://doi.org/10.1126/science.285.5428.747