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Cancer Cell. 2013 May 13;23(5):693-704. doi: 10.1016/j.ccr.2013.03.025.

Function of BRCA1 in the DNA damage response is mediated by ADP-ribosylation.

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1
Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

Abstract

Carriers of BRCA1 germline mutations are predisposed to breast and ovarian cancers. Accumulated evidence shows that BRCA1 is quickly recruited to DNA lesions and plays an important role in the DNA damage response. However, the mechanism by which BRCA1 is recruited to DNA damage sites remains elusive. BRCA1 forms a Ring-domain heterodimer with BARD1, a major partner of BRCA1 that contains tandem BRCA1 C-terminus (BRCT) motifs. Here, we identify the BRCTs of BARD1 as a poly(ADP-ribose) (PAR)-binding module. The binding of the BARD1 BRCTs to PAR targets the BRCA1/BARD1 heterodimer to DNA damage sites. Thus, our study uncovers a PAR-dependent mechanism of rapid recruitment of BRCA1/BARD1 to DNA damage sites.

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PMID:
23680151
PMCID:
PMC3759356
DOI:
10.1016/j.ccr.2013.03.025
[Indexed for MEDLINE]
Free PMC Article

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