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 language | English (US) |
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Article number | 1 |
Journal | Cell Division |
Volume | 9 |
Issue number | 1 |
DOIs | |
State | Published - Jul 9 2014 |
Externally published | Yes |
Keywords
- Cell cycle
- Chk1
- DNA repair
- Ubiquitination
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology