Mechanism of elimination of phosphorylated histone H2AX from chromatin after repair of DNA double-strand breaks.

ABSTRACT

Covalent modifications of histones in chromatin play an important role in regulation of eukaryotic gene expression and DNA repair. Formation of double-strand breaks (DSBs) in DNA is followed by the rapid local phosphorylation of the C-terminal serine in the replacement histone H2AX in megabase chromatin domains around DSBs and formation of discrete nuclear foci called gammaH2AX foci. This epigenetic modification of chromatin represents the "histone code" for DNA damage signaling and repair and has been extensively studied during last decade. It is known that after DSB rejoining gammaH2AX foci are eliminated from the nucleus, but molecular mechanism of this elimination remains to be established. However, gammaH2AX elimination can serve as a useful marker of DSB repair in normal cells and tissues. In this paper the available data on kinetics and possible mechanisms of gammaH2AX elimination are reviewed.