Binding of chromatin-modifying activities to phosphorylated histone H2A at DNA damage sites

Downs, Jessica A, Allard, Stéphane, Jobin-Robitaille, Olivier, Javaheri, Ali, Auger, Andréanne, Bouchard, Nathalie, Kron, Stephen J, Jackson, Stephen P and Côté, Jacques (2004) Binding of chromatin-modifying activities to phosphorylated histone H2A at DNA damage sites. Molecular Cell, 16 (6). pp. 979-990. ISSN 1097-2765

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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.

Item Type: Article
Additional Information: The work was initiated by JD, whoorganized the collaboration with the Cote lab. The design and interpretation of experiments and the manuscript preparation were done almost entirely by me and Prof. Cote. The data in approximately half of the figures in the manuscript were generated by JD.
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Jessica Downs
Date Deposited: 06 Feb 2012 21:12
Last Modified: 03 Apr 2012 10:39
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