TY - JOUR
T1 - Binding of chromatin-modifying activities to phosphorylated histone H2A at DNA damage sites
AU - Downs, Jessica A.
AU - Allard, Stéphane
AU - Jobin-Robitaille, Olivier
AU - Javaheri, Ali
AU - Auger, Andréanne
AU - Bouchard, Nathalie
AU - Kron, Stephen J.
AU - Jackson, Stephen P.
AU - Côté, Jacques
N1 - Funding Information:
We thank Nicolas Lacoste for performing important experiments linked to this project; Luc Galarneau for growth assays; and Nicolas Lacoste, Luc Galarneau, Rhea Utley, Amine Nourani, Dominique Cronier, Julie Savard, and Angélique Gagné-Henley for providing reagents. We are grateful to D. Stillman for anti-Arp4 and arp4-3/12/26 mutant strains, J. Haber for pGAL-HO and JKM115/JKM179 strains, Y. Makino for anti-Rvb1, M. Christman for YEP24-ARP4 vector, and J. Workman for anti-Tra1. We also thank F. Winston, S. Dent, L. Pillus, and U. Wintersberger for H2A-ΔN, H4-ΔN, esa1-Δ414/L254P, and arp4-S23A strains, respectively. This work was supported by grants from the Canadian Institutes of Health Research (CIHR) to J.C., Cancer Research UK to J.A.D./S.P.J., and Ludwig Fund for Cancer Research and NIH (R01 GM60443) to S.J.K. O.J.-R. and A.A. hold CIHR/Canadian Graduate Scholarship and National Science and Engineering Research Council scholarships, respectively. A.J. is supported by the University of Chicago Medical Scientist Training Program and an American Heart Association Greater Midwest predoctoral fellowship. J.A.D. is a Jenner Fellow of the Lister Institute, S.J.K. is a Leukemia and Lymphoma Society Scholar and J.C. is a CIHR Investigator.
PY - 2004/12/22
Y1 - 2004/12/22
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=10944267160&partnerID=8YFLogxK
U2 - 10.1016/j.molcel.2004.12.003
DO - 10.1016/j.molcel.2004.12.003
M3 - Article
C2 - 15610740
AN - SCOPUS:10944267160
VL - 16
SP - 979
EP - 990
JO - Molecular Cell
JF - Molecular Cell
SN - 1097-2765
IS - 6
ER -