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The ubiquitin specific protease USP34 promotes ubiquitin signaling at DNA double-strand breaks.

ABSTRACT: Ubiquitylation plays key roles in DNA damage signal transduction. The current model envisions that lysine63-linked ubiquitin chains, via the concerted action of E3 ubiquitin ligases RNF8-RNF168, are built at DNA double-strand breaks (DSBs) to effectively assemble DNA damage-repair factors for proper checkpoint control and DNA repair. We found that RNF168 is a short-lived protein that is stabilized by the deubiquitylating enzyme USP34 in response to DNA damage. In the absence of USP34, RNF168 is rapidly degraded, resulting in attenuated DSB-associated ubiquitylation, defective recruitment of BRCA1 and 53BP1 and compromised cell survival after ionizing radiation. We propose that USP34 promotes a feed-forward loop to enforce ubiquitin signaling at DSBs and highlight critical roles of ubiquitin dynamics in genome stability maintenance.

SUBMITTER: Sy SM

PROVIDER: S-EPMC3794584 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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The ubiquitin specific protease USP34 promotes ubiquitin signaling at DNA double-strand breaks.

Sy Shirley M H SM Jiang Jun J O Wai Sum WS Deng Yiqun Y Huen Michael S Y MS

Nucleic acids research 20130717 18

Ubiquitylation plays key roles in DNA damage signal transduction. The current model envisions that lysine63-linked ubiquitin chains, via the concerted action of E3 ubiquitin ligases RNF8-RNF168, are built at DNA double-strand breaks (DSBs) to effectively assemble DNA damage-repair factors for proper checkpoint control and DNA repair. We found that RNF168 is a short-lived protein that is stabilized by the deubiquitylating enzyme USP34 in response to DNA damage. In the absence of USP34, RNF168 is ...[more]

PMID: 23863847

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