title: Binding of chromatin-modifying activities to phosphorylated histone H2A at DNA damage sites.
abstract: Yeast histone H2A is phosphorylated on Ser129 upon DNA damage, an event required for efficient repair. We show that phosphorylation occurs rapidly over a large region around DNA double-strand breaks (DSBs). Histone H4 acetylation is also important for DSB repair, and we found that the NuA4 HAT complex associates specifically with phospho-H2A peptides. A single NuA4 subunit, Arp4, is responsible for the interaction. The NuA4 complex is recruited to a DSB concomitantly with the appearance of H2A P-Ser129 and Arp4 is important for this binding. Arp4 is also a subunit of the Ino80 and Swr1 chromatin remodeling complexes, which also interact with H2A P-Ser129 and are recruited to DSBs. This association again requires Arp4 but also prior NuA4 recruitment and action. Thus, phosphorylation of H2A at DNA damage sites creates a mark recognized by different chromatin modifiers. This interaction leads to stepwise chromatin reconfiguration, allowing efficient DNA repair.
authors.affiliation: The Wellcome Trust/Cancer Research UK Gurdon Institute and Department of Zoology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR, United Kingdom. jad32@mole.bio.cam.ac.uk
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Downs
authors.forename: Stéphane
authors.initials: S
authors.lastname: Allard
authors.forename: Olivier
authors.initials: O
authors.lastname: Jobin-Robitaille
authors.forename: Ali
authors.initials: A
authors.lastname: Javaheri
authors.forename: Andréanne
authors.initials: A
authors.lastname: Auger
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bouchard
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kron
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Jackson
authors.forename: Jacques
authors.initials: J
authors.lastname: Côté
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly / Q000502:physiology; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology*; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism*; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism; D015003:Yeasts / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D006657:Histones; D012694:Serine; D004247:DNA; D000123:Acetyltransferases; D051548:Histone Acetyltransferases