Host: The Japan Radiation Research Society, Chairman of the 52nd Annual Meeting, Toshiteru Okubo (Radiation Effects Research Foundation)
Recruitment of DNA repair factors and checkpoint proteins is important step for DNA damage response. Chromatin reorganization involving histone modifications, histone variant exchange, histone eviction and nucleosome remodeling is required for DNA repair factors to access DNA damage sites. However, it still remains largely unclear how chromatin reorganization is coupled with the initiation of DNA repair process and the activation of checkpoint machinery immediately after DNA damage. We have already shown that histone H2AX is rapidly evicted from chromatin after induction of DNA damage. Analysis of purified H2AX complex revealed that DNA damage induced the acetylation and ubiquitination of H2AX in addition to the phosphorylation. Interestingly, the eviction of H2AX depends not on phosphorylation, but rather on acetylation by TIP60 histone acetylase, an enzyme involved in DNA repair, and ubiquitination. In addition to these findings, we found that acetylation of H2AX by TIP60 is necessary for the binding of NBS1 and ATM with the damaged chromatin. We will discuss about the crosstalk between H2AX eviction via histone acetylation and checkpoint activation during the DNA damage response.
