Dynamics of histone H2AX in DNA damage response

抄録

Eukaryotic genome is the tightly packed into the chromatin, a hierarchically organized complex of DNA and histone and nonhistone proteins. This packing represents a common obstacle for most of the DNA functions. We have already shown that TIP60 histone acetylase complex involved in DNA repair and apoptosis. However, it remains unknown how TIP60 complex involve in DNA repair. To better understand the mechanism of TIP60 complex in DNA repair, TIP60 complex purifies from chromatin soluble fraction after DNA damage. As a result, the TIP60 complex is associated with g-H2AX after DNA damage. Histone H2AX, histone H2A variant, is phosphorylated at the site of DNA double-strand breaks (DSBs). Furthermore, it has been revealed that H2AX is highly mobile upon DSBs in the nucleus in the experiment of the Photo-bleaching with micro-irradiation. Interestingly, in mutated TIP60 (which is lack of histone acetylase activity) expressing human fibroblast cells, the dynamics of H2AX is inhibited upon DSBs relative to parental human fibroblast cells. Thus TIP60 complex regulates the dynamics of H2AX after induction of DNA damage. These results indicate that dynamics of H2AX might have important implications for initial DNA repair process.