Ubiquitin-specific protease 5 is required for the efficient repair of DNA double-strand breaks

Satoshi Nakajima, Li Lan, Leizhen Wei, Ching Lung Hsieh, Vesna Rapić-Otrin, Akira Yasui, Arthur S. Levine

    Research output: Contribution to journalArticlepeer-review

    38 Citations (Scopus)


    During the DNA damage response (DDR), ubiquitination plays an important role in the recruitment and regulation of repair proteins. However, little is known about elimination of the ubiquitination signal after repair is completed. Here we show that the ubiquitin-specific protease 5 (USP5), a deubiquitinating enzyme, is involved in the elimination of the ubiquitin signal from damaged sites and is required for efficient DNA double-strand break (DSB) repair. Depletion of USP5 sensitizes cells to DNA damaging agents, produces DSBs, causes delayed disappearance of γH2AX foci after Bleocin treatment, and influences DSB repair efficiency in the homologous recombination pathway but not in the non-homologous end joining pathway. USP5 co-localizes to DSBs induced by laser micro-irradiation in a RAD18-dependent manner. Importantly, polyubiquitin chains at sites of DNA damage remained for longer periods in USP5-depleted cells. Our results show that disassembly of polyubiquitin chains by USP5 at sites of damage is important for efficient DSB repair.

    Original languageEnglish
    Article numbere84899
    JournalPloS one
    Issue number1
    Publication statusPublished - 2014 Jan 14

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Agricultural and Biological Sciences(all)
    • General


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