RAP80 Targets BRCA1 to Specific Ubiquitin Structures at DNA Damage Sites

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 lysine6- 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.

• Publication year

  2007

• Venue

  Science

• Publication date

  2007-05-25

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1126/science.1139516PMID 17525341PMCID PMC2706583
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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