Regulation of mec1 kinase activity by the SWI/SNF chromatin remodeling complex

Prabodh Kapoor, Yunhe Bao, Jing Xiao, Jie Luo, Jianfeng Shen, Jim Persinger, Guang Peng, Jeff Ranish, Blaine Bartholomew, Xuetong Shen

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

ATP-dependent chromatin remodeling complexes alter chromatin structure through interactions with chromatin substrates such as DNA, histones, and nucleosomes. However, whether chromatin remodeling complexes have the ability to regulate nonchromatin substrates remains unclear. Saccharomyces cerevisiae checkpoint kinase Mec1 (ATR in mammals) is an essential master regulator of genomic integrity. Here we found that the SWI/SNF chromatin remodeling complex is capable of regulating Mec1 kinase activity. In vivo, Mec1 activity is reduced by the deletion of Snf2, the core ATPase subunit of the SWI/SNF complex. SWI/SNF interacts with Mec1, and cross-linking studies revealed that the Snf2 ATPase is the main interaction partner for Mec1. In vitro, SWI/SNF can activate Mec1 kinase activity in the absence of chromatin or known activators such as Dpb11. The subunit requirement of SWI/SNFmediated Mec1 regulation differs from that of SWI/SNF-mediated chromatin remodeling. Functionally, SWI/SNFmediated Mec1 regulation specifically occurs in S phase of the cell cycle. Together, these findings identify a novel regulator of Mec1 kinase activity and suggest that ATP-dependent chromatin remodeling complexes can regulate nonchromatin substrates such as a checkpoint kinase.

Original languageEnglish (US)
Pages (from-to)591-602
Number of pages12
JournalGenes and Development
Volume29
Issue number6
DOIs
StatePublished - 2015

Keywords

  • ATR
  • Checkpoint regulation
  • Chromatin remodeling
  • Mec1
  • SWI/SNF

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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