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

Mol Cell. 2004 Dec 22;16(6):979-90. doi: 10.1016/j.molcel.2004.12.003.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetyltransferases / metabolism
  • Chromatin / metabolism*
  • Chromatin Assembly and Disassembly / physiology
  • DNA / metabolism*
  • DNA Damage / physiology*
  • DNA Repair / physiology*
  • Histone Acetyltransferases
  • Histones / metabolism*
  • Phosphorylation
  • Serine / metabolism
  • Yeasts / genetics
  • Yeasts / metabolism

Substances

  • Chromatin
  • Histones
  • Serine
  • DNA
  • Acetyltransferases
  • Histone Acetyltransferases