Article
- The EMBO Journal (2007) 26, 4113 - 4125
- doi:10.1038/sj.emboj.7601835
Published online: 30 August 2007
Subject Categories:
Distinct roles for SWR1 and INO80 chromatin remodeling complexes at chromosomal double-strand breaks
Haico van Attikum1,a, Olivier Fritsch1,b and Susan M Gasser1
- Division of Epigenetics, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
Correspondence to:
Susan M Gasser, Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, Basel-4058, Switzerland. Tel.: +41 61 697 7255; Fax: +41 61 697 3976; E-mail: susan.gasser@fmi.ch
aPresent address: Department of Toxicogenetics, Leiden University Medical Center, Einthovenweg 20, Leiden 2333, The Netherlands
bPresent address: Department of Biological Clinical Sciences, Centre for Biomedicine, University of Basel, Basel-4058, Switzerland
Received 3 May 2007; Accepted 1 August 2007
Abstract
INO80 and SWR1 are two closely related ATP-dependent chromatin remodeling complexes that share several subunits. Ino80 was reported to be recruited to the HO endonuclease-induced double-strand break (DSB) at the budding yeast mating-type locus, MAT. We find Swr1 similarly recruited in a manner dependent on the phosphorylation of H2A (
H2AX). This is not unique to cleavage at MAT; both Swr1 and Ino80 bind near an induced DSB on chromosome XV. Whereas Swr1 incorporates the histone variant H2A.Z into chromatin at promoters, H2A.Z levels do not increase at DSBs. Instead, H2A.Z, H2AX and core histones are coordinately removed near the break in an INO80-dependent, but SWR1-independent, manner. Mutations in INO80-specific subunits Arp8 or Nhp10 impair the binding of Mre11 nuclease, yKu80 and ATR-related Mec1 kinase at the DSB, resulting in defective end-processing and checkpoint activation. In contrast, Mre11 binding, end-resection and checkpoint activation were normal in the swr1 strain, but yKu80 loading and error-free end-joining were impaired. Thus, these two related chromatin remodelers have distinct roles in DSB repair and checkpoint activation.
Keywords:
- checkpoint,
- chromatin,
- DSB repair,
- INO80,
- SWR1
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