title: Regulation of Mec1 kinase activity by the SWI/SNF chromatin remodeling complex.
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/SNF-mediated Mec1 regulation differs from that of SWI/SNF-mediated chromatin remodeling. Functionally, SWI/SNF-mediated 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.
authors: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Smithville, Texas 78957, USA;
authors: Prabodh
authors: P
authors: Kapoor
authors: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Smithville, Texas 78957, USA;
authors: Yunhe
authors: Y
authors: Bao
authors: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Smithville, Texas 78957, USA;
authors: Jing
authors: J
authors: Xiao
authors: Institute for Systems Biology, Seattle, Washington 98109, USA;
authors: Jie
authors: J
authors: Luo
authors: Department of Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Jianfeng
authors: J
authors: Shen
authors: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Smithville, Texas 78957, USA;
authors: Jim
authors: J
authors: Persinger
authors: Department of Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Guang
authors: G
authors: Peng
authors: Institute for Systems Biology, Seattle, Washington 98109, USA;
authors: Jeff
authors: J
authors: Ranish
authors: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Smithville, Texas 78957, USA;
authors: Blaine
authors: B
authors: Bartholomew
authors: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Smithville, Texas 78957, USA; snowshen@mac.com.
authors: Xuetong
authors: X
authors: Shen
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004249:DNA Damage / Q000502:physiology; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D020536:Enzyme Activators; D047908:Intracellular Signaling Peptides and Proteins; C445179:SWI-SNF-B chromatin-remodeling complex; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D000251:Adenosine Triphosphatases; C499333:SNF2 protein, S cerevisiae
keywords: ATR; Mec1; SWI/SNF; checkpoint regulation; chromatin remodeling