The DNA repair component Metnase regulates Chk1 stability

Elizabeth A. Williamson, Yuehan Wu, Sudha Singh, Michael Byrne, Justin Wray, Suk Hee Lee, Jac A. Nickoloff, Robert Hromas

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Chk1 both arrests replication forks and enhances repair of DNA damage by phosphorylation of downstream effectors. Metnase (also termed SETMAR) is a SET histone methylase and transposase nuclease protein that promotes both DNA double strand break (DSB) repair and re-start of stalled replication forks. We previously found that Chk1 phosphorylation of Metnase on S495 enhanced its DNA DSB repair activity but decreased its ability to re-start stalled replication forks. Here we show that phosphorylated Metnase feeds back to increase the half-life of Chk1. Chk1 half-life is regulated by DDB1 targeting it to Cul4A for ubiquitination and destruction. Metnase decreases Chk1 interaction with DDB1, and decreases Chk1 ubiquitination. These data define a novel pathway for Chk1 regulation, whereby a target of Chk1, Metnase, feeds back to amplify Chk1 stability, and therefore enhance replication fork arrest.

Original languageEnglish (US)
Article number1
JournalCell Division
Volume9
Issue number1
DOIs
StatePublished - Jul 9 2014

Keywords

  • Cell cycle
  • Chk1
  • DNA repair
  • Ubiquitination

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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