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 journalArticle

4 Citations (Scopus)

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
Article number1
JournalCell Division
Volume9
Issue number1
DOIs
StatePublished - Jul 9 2014

Fingerprint

Double-Stranded DNA Breaks
Ubiquitination
DNA Repair
Half-Life
Phosphorylation
Repair
Transposases
DNA
DNA Damage
Proteins
histone methyltransferase

Keywords

  • Cell cycle
  • Chk1
  • DNA repair
  • Ubiquitination

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Cite this

Williamson, E. A., Wu, Y., Singh, S., Byrne, M., Wray, J., Lee, S-H., ... Hromas, R. (2014). The DNA repair component Metnase regulates Chk1 stability. Cell Division, 9(1), [1]. https://doi.org/10.1186/1747-1028-9-1

The DNA repair component Metnase regulates Chk1 stability. / Williamson, Elizabeth A.; Wu, Yuehan; Singh, Sudha; Byrne, Michael; Wray, Justin; Lee, Suk-Hee; Nickoloff, Jac A.; Hromas, Robert.

In: Cell Division, Vol. 9, No. 1, 1, 09.07.2014.

Research output: Contribution to journalArticle

Williamson, EA, Wu, Y, Singh, S, Byrne, M, Wray, J, Lee, S-H, Nickoloff, JA & Hromas, R 2014, 'The DNA repair component Metnase regulates Chk1 stability', Cell Division, vol. 9, no. 1, 1. https://doi.org/10.1186/1747-1028-9-1
Williamson EA, Wu Y, Singh S, Byrne M, Wray J, Lee S-H et al. The DNA repair component Metnase regulates Chk1 stability. Cell Division. 2014 Jul 9;9(1). 1. https://doi.org/10.1186/1747-1028-9-1
Williamson, Elizabeth A. ; Wu, Yuehan ; Singh, Sudha ; Byrne, Michael ; Wray, Justin ; Lee, Suk-Hee ; Nickoloff, Jac A. ; Hromas, Robert. / The DNA repair component Metnase regulates Chk1 stability. In: Cell Division. 2014 ; Vol. 9, No. 1.
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