title: 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.
authors.affiliation: Genome Stability Research Laboratory, The University of Hong Kong, Hong Kong, People's Republic of China, Department of Anatomy, The University of Hong Kong, Hong Kong, People's Republic of China, Center for Cancer Research, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China, Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, College of Life Sciences, South China Agricultural University, Guangzhou, Guangdong 510642, China and State Key Laboratory of Brain and Cognitive Science, The University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Shirley M H
authors.initials: SM
authors.lastname: Sy
authors.forename: Jun
authors.initials: J
authors.lastname: Jiang
authors.forename: Wai Sum
authors.initials: WS
authors.lastname: O
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Deng
authors.forename: Michael S Y
authors.initials: MS
authors.lastname: Huen
mesh_terms: D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004795:Enzyme Stability; D057809:HEK293 Cells; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D064570:Ubiquitin-Specific Proteases / Q000032:analysis / Q000502:physiology*; D054875:Ubiquitination
chemical_list: D006657:Histones; C535210:RNF168 protein, human; D044767:Ubiquitin-Protein Ligases; C584673:USP34 protein, human; D064570:Ubiquitin-Specific Proteases