Abstract
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. The role of these chromatin modifications in the cellular response to DNA damage remains largely unexplored. Recently,we revealed that the TIP60 histone acetylase complex involved in DNA repair and apoptosis. However,it remains unknown how the TIP60 complex involves in DNA repair. To better understand the mechanism of the TIP60 complex in DNA repair, the TIP60 complex purifies from chromatin soluble fraction after DNA damage. As a result, TIP60 complex is associated with gamma- H2AX after DNA damage. Histone H2AX is histone H2A variant and double strand breaks(DSBs)induce phosphorylation of histone H2AX. We investigated the relationship between the phosphorylation of H2AX and the HAT activity of the TIP60 complex. As a result,in mutated TIP60 expressing HeLa cells,the amount of the phosphorylation of histone H2AX was reduced compared with the parental Hela cells after DNA damage. Thus,the phosphorylation of H2AX required for the HAT activity of the TIP60 complex. In this talk,I would like to discuss the role of the TIP60 HAT complex in DNA repair focusing on histone H2AX.
