Williamson, Elizabeth A.Wu, YuehanSingh, SudhaByrne, MichaelWray, JustinLee, Suk-HeeNickoloff, Jac A.Hromas, Robert2025-04-022025-04-022014-07-09Williamson EA, Wu Y, Singh S, et al. The DNA repair component Metnase regulates Chk1 stability. Cell Div. 2014;9:1. Published 2014 Jul 9. doi:10.1186/1747-1028-9-1https://hdl.handle.net/1805/46752Chk1 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.en-USAttribution 4.0 InternationalDNA repairChk1UbiquitinationCell cycleArticle