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BRCA1 ubiquitinates its phosphorylation-dependent binding partner CtIP.

Xiaochun Yu·Shuang Fu·Maoyi Lai·Richard Baer·Junjie Chen
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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.

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BRCA1 ProteinCarrier ProteinsCatalysisCell CycleCell LineChromatinDNA DamageEndodeoxyribonucleasesHumansNuclear ProteinsPhosphorylationProteasome Endopeptidase ComplexProtein BindingProtein Structure, TertiarySerineSignal TransductionUbiquitin-Protein LigasesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.

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Xiaochun Yu, Shuang Fu, Maoyi Lai, Richard Baer, Junjie Chen. 2006-07-01. BRCA1 ubiquitinates its phosphorylation-dependent binding partner CtIP.. https://doi.org/10.1101/gad.1431006

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