Host: The Japan Radiation Research Society
DNA double-strand breaks (DSB) are serious damage which leads to genomic instability or cell death. Hence, mammalian cells recognize DSBs immediately and repair them when they are generated into genome DNA.
Since genome DNA is compacted into chromatin structure with histone protein in higher eukaryotic cells, the chromatin structure might be remodeled to recognize and repair the damaged DNA with specific modifications of histones. The phosphorylation of histone H2AX is one of important modification in response to DNA damage. Histone H2AX is a variant of histone H2A in higher eukaryote and the C-terminus of histone H2AX is phosphorylated in response to generation of DSB. This phosphorylation is indispensable for the recruitment of DNA damage-related proteins to DSB sites.
In addition, the amino acid sequence of histone H2AX suggests acetylation, ubiquitylation and sumoylation of histone H2AX and these modification may be included in DNA damage response. Therefore, we investigated the role of histone H2AX in DSB-induced damage response.
When we analyzed the phosphorylation of histone H2AX after exposure to ionizing radiation(IR), two extra-bands were detected by g-H2AX andibody. Histone H2AX is also sumoylated in N-terminus in vitro assay. Moreover, we detected that histone H2AX was acetylated on N-terminus using anti-acetyl histone H2A antibody. Thus, histone H2AX might be modified in several manners following DNA damage. We discuss the role of these modification in IR-induced foci formation and DSB repair.
