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-γH2AX-dependent lysine 6- and lysine63-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.
Original language | English |
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Pages (from-to) | 1198-1202 |
Number of pages | 5 |
Journal | Science |
Volume | 316 |
Issue number | 5828 |
DOIs | |
Publication status | Published - 25 May 2007 |
Externally published | Yes |