Journal
GENES & DEVELOPMENT
Volume 20, Issue 13, Pages 1721-1726Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1431006
Keywords
BRCA1; CtIP; ubiquitination; DNA damage; phosphorylation; BRCT domain
Categories
Funding
- NCI NIH HHS [R01 CA089239, CA97403, CA89239, P01 CA097403] Funding Source: Medline
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BRCA1 (Breast Cancer Susceptibility Gene 1) possesses an N-terminal Ring domain and tandem C-terminal BRCT motifs. While the Ring domain has E3 ubiquitin ligase activity, the BRCA1 BRCT domains specifically recognize phospho-serine motifs. Here, we demonstrate that BRCA1 Ring domain catalyzes CtIP ubiquitination in a manner that depends on a phosphorylation-mediated interaction between CtIP and BRCA1 BRCT domains. The BRCA1-dependent ubiquitination of CtIP does not target CtIP for degradation. Instead, ubiquitinated CtIP associates with chromatin following DNA damage and participates in G2/M checkpoint control. Thus, we propose that BRCA1 can regulate the functions of its substrates through nonproteasomal pathways that do not involve substrate degradation.
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