RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage sites

  • Science. 2007 May 25;316(5828):1198-202. doi: 10.1126/science.1139516.
Bijan Sobhian  1 ,  Genze Shao ,  Dana R Lilli ,  Aedín C Culhane ,  Lisa A Moreau ,  Bing Xia ,  David M Livingston ,  Roger A Greenberg
Affiliations
  • 1. Dana-Farber Cancer Institute and Department of Genetics and Department of Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
PMID: 17525341 DOI: 10.1126/science.1139516
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.