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HERC2-USP20 axis regulates DNA damage checkpoint through Claspin.

ABSTRACT: The DNA damage response triggers cell-cycle checkpoints, DNA repair and apoptosis using multiple post-translational modifications as molecular switches. However, how ubiquitination regulates ATR signaling in response to replication stress and single-strand break is still unclear. Here, we identified the deubiquitination enzyme (DUB) USP20 as a pivotal regulator of ATR-related DDR pathway. Through screening a panel of DUBs, we identified USP20 as critical for replication stress response. USP20 is phosphorylated by ATR, resulting in disassociation of the E3 ubiquitin ligase HERC2 from USP20 and USP20 stabilization. USP20 in turn deubiquitinates and stabilizes Claspin and enhances the activation of ATR-Chk1 signaling. These findings reveal USP20 to be a novel regulator of ATR-dependent DNA damage signaling.

SUBMITTER: Yuan J

PROVIDER: S-EPMC4245938 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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HERC2-USP20 axis regulates DNA damage checkpoint through Claspin.

Yuan Jian J Luo Kuntian K Deng Min M Li Yunhui Y Yin Ping P Gao Bowen B Fang Yuan Y Wu Puqiang P Liu Tongzheng T Lou Zhenkun Z

Nucleic acids research 20141029 21

The DNA damage response triggers cell-cycle checkpoints, DNA repair and apoptosis using multiple post-translational modifications as molecular switches. However, how ubiquitination regulates ATR signaling in response to replication stress and single-strand break is still unclear. Here, we identified the deubiquitination enzyme (DUB) USP20 as a pivotal regulator of ATR-related DDR pathway. Through screening a panel of DUBs, we identified USP20 as critical for replication stress response. USP20 is ...[more]

PMID: 25355518

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