title: Histone degradation in response to DNA damage enhances chromatin dynamics and recombination rates.
abstract: Nucleosomes are essential for proper chromatin organization and the maintenance of genome integrity. Histones are post-translationally modified and often evicted at sites of DNA breaks, facilitating the recruitment of repair factors. Whether such chromatin changes are localized or genome-wide is debated. Here we show that cellular levels of histones drop 20-40% in response to DNA damage. This histone loss occurs from chromatin, is proteasome-mediated and requires both the DNA damage checkpoint and the INO80 nucleosome remodeler. We confirmed reductions in histone levels by stable isotope labeling of amino acids in cell culture (SILAC)-based mass spectrometry, genome-wide nucleosome mapping and fluorescence microscopy. Chromatin decompaction and increased fiber flexibility accompanied histone degradation, both in response to DNA damage and after artificial reduction of histone levels. As a result, recombination rates and DNA-repair focus turnover were enhanced. Thus, we propose that a generalized reduction in nucleosome occupancy is an integral part of the DNA damage response in yeast that provides mechanisms for enhanced chromatin mobility and homology search.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.|Faculty of Natural Sciences, University of Basel, Basel, Switzerland.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Hauer
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.|Faculty of Natural Sciences, University of Basel, Basel, Switzerland.
authors.forename: Andrew
authors.initials: A
authors.lastname: Seeber
authors.affiliation: Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee, UK.
authors.forename: Vijender
authors.initials: V
authors.lastname: Singh
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Raphael
authors.initials: R
authors.lastname: Thierry
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Ragna
authors.initials: R
authors.lastname: Sack
authors.affiliation: Institut de Biologie de l'École Normale Supérieure, Ecole Normale Supérieure, Paris, France.
authors.forename: Assaf
authors.initials: A
authors.lastname: Amitai
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Mariya
authors.initials: M
authors.lastname: Kryzhanovska
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Jan
authors.identifier: 0000-0001-7234-1435
authors.initials: J
authors.lastname: Eglinger
authors.affiliation: Institut de Biologie de l'École Normale Supérieure, Ecole Normale Supérieure, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Holcman
authors.affiliation: Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee, UK.
authors.forename: Tom
authors.initials: T
authors.lastname: Owen-Hughes
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.|Faculty of Natural Sciences, University of Basel, Basel, Switzerland.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Gasser
mesh_terms: D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D004249:DNA Damage; D004260:DNA Repair; D006657:Histones / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D002843:Chromatin; D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; D046988:Proteasome Endopeptidase Complex