title: Distinct roles for SWR1 and INO80 chromatin remodeling complexes at chromosomal double-strand breaks.
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 (gammaH2AX). 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, gammaH2AX 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.
authors.affiliation: Division of Epigenetics, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Haico
authors.initials: H
authors.lastname: van Attikum
authors.forename: Olivier
authors.initials: O
authors.lastname: Fritsch
authors.forename: Susan M
authors.initials: SM
authors.lastname: Gasser
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D015825:Chromosomes, Fungal / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004271:DNA, Fungal / Q000378:metabolism; D017353:Gene Deletion; D006657:Histones / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D004271:DNA, Fungal; D006657:Histones; C493530:Htz1 protein, S cerevisiae; C483404:INO80 complex, S cerevisiae; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; C507778:gammaH2AX protein, S cerevisiae; D000251:Adenosine Triphosphatases; C481261:Swr1 protein, S cerevisiae