TY - JOUR
T1 - Regulation of mec1 kinase activity by the SWI/SNF chromatin remodeling complex
AU - Kapoor, Prabodh
AU - Bao, Yunhe
AU - Xiao, Jing
AU - Luo, Jie
AU - Shen, Jianfeng
AU - Persinger, Jim
AU - Peng, Guang
AU - Ranish, Jeff
AU - Bartholomew, Blaine
AU - Shen, Xuetong
N1 - Publisher Copyright:
© 2015 Tycowski et al.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - ATR
KW - Checkpoint regulation
KW - Chromatin remodeling
KW - Mec1
KW - SWI/SNF
UR - http://www.scopus.com/inward/record.url?scp=84925248811&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84925248811&partnerID=8YFLogxK
U2 - 10.1101/gad.257626.114
DO - 10.1101/gad.257626.114
M3 - Article
C2 - 25792597
AN - SCOPUS:84925248811
SN - 0890-9369
VL - 29
SP - 591
EP - 602
JO - Genes and Development
JF - Genes and Development
IS - 6
ER -