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Science. 2007 May 25;316(5828):1198-202.

RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage sites.

Author information

1
Dana-Farber Cancer Institute and Department of Genetics and Department of Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.

Abstract

Mutations affecting the BRCT domains of the breast cancer-associated tumor suppressor BRCA1 disrupt the recruitment of this protein to DNA double-strand breaks (DSBs). The molecular structures at DSBs recognized by BRCA1 are presently unknown. We report the interaction of the BRCA1 BRCT domain with RAP80, a ubiquitin-binding protein. RAP80 targets a complex containing the BRCA1-BARD1 (BRCA1-associated ring domain protein 1) E3 ligase and the deubiquitinating enzyme (DUB) BRCC36 to MDC1-gammaH2AX-dependent lysine(6)- and lysine(63)-linked ubiquitin polymers at DSBs. These events are required for cell cycle checkpoint and repair responses to ionizing radiation, implicating ubiquitin chain recognition and turnover in the BRCA1-mediated repair of DSBs.

PMID:
17525341
PMCID:
PMC2706583
DOI:
10.1126/science.1139516
[Indexed for MEDLINE]
Free PMC Article
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