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Regulation of Mec1 kinase activity by the SWI/SNF chromatin remodeling complex
Prabodh Kapoor1, Yunhe Bao1, Jing Xiao1
1Department of Epigenetics and Molecular Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Smithville, Texas 78957, USA;
Genes & Development
|March 21, 2015
Summary
The SWI/SNF chromatin remodeling complex regulates the Mec1 checkpoint kinase, a novel function beyond chromatin. This interaction is crucial for genomic integrity during S phase.
Area of Science:
- Cellular Biology
- Molecular Biology
- Biochemistry
Background:
- ATP-dependent chromatin remodeling complexes modify chromatin structure.
- The role of these complexes in regulating non-chromatin substrates is largely unknown.
- Mec1 (ATR in mammals) is a key regulator of genomic integrity.
Purpose of the Study:
- To investigate whether chromatin remodeling complexes can regulate non-chromatin substrates.
- To determine if the SWI/SNF complex interacts with and regulates Mec1 kinase activity.
Main Methods:
- In vivo studies in Saccharomyces cerevisiae.
- Biochemical assays including cross-linking studies.
- In vitro kinase assays.
Main Results:
- Deletion of Snf2, a SWI/SNF subunit, reduced Mec1 activity in vivo.
- SWI/SNF directly interacts with Mec1, with Snf2 as the primary partner.
- SWI/SNF activates Mec1 kinase activity in vitro, independent of chromatin.
- Regulation of Mec1 by SWI/SNF occurs specifically in S phase and has different subunit requirements than chromatin remodeling.
Conclusions:
- The SWI/SNF complex regulates Mec1 kinase activity, a novel non-chromatin function.
- This finding expands the known roles of ATP-dependent chromatin remodeling complexes.
- SWI/SNF acts as a novel regulator of Mec1, impacting genomic integrity.
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