The DNA repair component Metnase regulates Chk1 stability

被引：8

作者：

Williamson, Elizabeth A. ^{[1
]}

Wu, Yuehan ^{[1
]}

Singh, Sudha ^{[1
]}

Byrne, Michael ^{[1
]}

Wray, Justin ^{[1
]}

Lee, Suk-Hee ^{[2
]}

Nickoloff, Jac A. ^{[3
]}

Hromas, Robert ^{[1
]}

机构：

[1] Univ Florida, Coll Med, Dept Med, Gainesville, FL 32610 USA

[2] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA

[3] Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA

来源：

CELL DIVISION | 2014年 / 9卷

关键词：

DNA repair; Chk1; Ubiquitination; Cell cycle; TRANSPOSASE DOMAIN; NHEJ REPAIR; RESTART; SET;

D O I：

10.1186/1747-1028-9-1

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：4

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