Abstract
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.
Original language | English (US) |
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Pages (from-to) | 1721-1726 |
Number of pages | 6 |
Journal | Genes and Development |
Volume | 20 |
Issue number | 13 |
DOIs | |
State | Published - Jul 1 2006 |
Externally published | Yes |
Keywords
- BRCA1
- BRCT domain
- CtIP
- DNA damage
- Phosphorylation
- Ubiquitination
ASJC Scopus subject areas
- Genetics
- Developmental Biology