Binding of chromatin-modifying activities to phosphorylated histone H2A at DNA damage sites.
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.
Downs
Jessica A
JA
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
Allard
Stéphane
S
Jobin-Robitaille
Olivier
O
Javaheri
Ali
A
Auger
Andréanne
A
Bouchard
Nathalie
N
Kron
Stephen J
SJ
Jackson
Stephen P
SP
Côté
Jacques
J
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
D002843:Chromatin; D006657:Histones; D012694:Serine; D004247:DNA; D000123:Acetyltransferases; D051548:Histone Acetyltransferases