HERC2-USP20 axis regulates DNA damage checkpoint through Claspin

Jian Yuan, Kuntian Luo, Min Deng, Yunhui Li, Ping Yin, Bowen Gao, Yuan Fang, Puqiang Wu, Tongzheng Liu, Zhenkun Lou

Research output: Contribution to journalArticle

40 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)13110-13121
Number of pages12
JournalNucleic acids research
Volume42
Issue number21
DOIs
StatePublished - Dec 1 2014

ASJC Scopus subject areas

  • Genetics

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    Yuan, J., Luo, K., Deng, M., Li, Y., Yin, P., Gao, B., Fang, Y., Wu, P., Liu, T., & Lou, Z. (2014). HERC2-USP20 axis regulates DNA damage checkpoint through Claspin. Nucleic acids research, 42(21), 13110-13121. https://doi.org/10.1093/nar/gku1034