title: INO80-C and SWR-C: guardians of the genome.
abstract: The double membrane of the eukaryotic nucleus surrounds the genome, constraining it to a nuclear sphere. Proteins, RNA protein particles and artificial chromosome rings diffuse rapidly and freely throughout the nucleoplasm, while chromosomal loci show subdiffusive movement with varying degrees of constraint. In situ biochemical approaches and live imaging studies have revealed the existence of nuclear subcompartments that are enriched for specific chromatin states and/or enzymatic activities. This sequestration is thought to enhance the formation of heterochromatin, particularly when factors of limited abundance are involved. Implicit in the concept of compartmentation is the idea that chromatin is able to move from one compartment to another. Indeed, in budding yeast, gene activation, repression and the presence of persistent DNA double-strand breaks each has been shown to provoke subnuclear relocalization of chromatin. In some cases, movement has been linked to the action of ATP-dependent chromatin remodeling complexes, more specifically to the Snf2-related ATPase-containing complexes, SWR-C and INO80-C. Here we examine how these multi-subunit remodelers contribute to chromatin-based processes linked to the DNA damage response. We review recent evidence that supports a role for yeast SWR-C and INO80-C in determining the subnuclear position of damaged domains and finally, we recap the multiple ways in which these remodelers contribute to genomic integrity.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
authors.forename: Christian-Benedikt
authors.initials: CB
authors.lastname: Gerhold
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Hauer
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland; University of Basel Faculty of Natural Sciences, Klingelbergstrasse 50, CH-4056 Basel, Switzerland. Electronic address: susan.gasser@fmi.ch.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Gasser
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000235:genetics*; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D016681:Genome, Fungal; D009707:Nucleosomes / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C483404:INO80 complex, S cerevisiae; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; D000251:Adenosine Triphosphatases; C481261:Swr1 protein, S cerevisiae
keywords: DNA repair; INO80-C; SWR-C; chromatin remodeling; nuclear organization