Host: The Japan Radiation Research Society
Co-host: Asian Association for Radiation Research
Radiation-induced DNA double strand breaks (DSBs) are recognised by ATM and activated ATM then phsophorylates and activates downstream factors such as histone H2AX. In irradiated interphase cells, phosphorylated histone H2AX foci, which appear immediately after irradiation, colocalise with proteins involved in DNA damage repair. Therefore they are thought to represent DSBs and have a role in DNA damage repair. However, we have found that phospho-H2AX foci are formed at sites of DSB as well as at sites of chromatin aberrations without DSBs. This study aimed to elucidate a possible new role of radiation-induced phosphorylation of H2AX. First, behaviors of phospho-H2AX, phospho-ATM and 53BP1 in irradiated mitotic-phase cells were analysed. In response to X-ray irradiation, phospho-H2AX formed foci in all mitotic-phase cells while phospho-ATM and 53BP1 did not. When these cells successfully divided and progressed to G1-phase, the three proteins formed foci and they colocalised. The results obtained differed from the fact that the proteins colocalise in irradiated interphase cells. This suggests a possible new role for phosphorylated H2AX foci. Since DSBs are lethal in mitotic cells, the phospho-H2AX foci observed in surviving G1 cells are thought to represent the sites of chromatin aberrations without DSBs. Therefore phosphorylation of histone H2AX might have a role in recruiting mediators such as phosphorylated ATM and 53BP1 to the sites of chromatin aberrations not accompanying DSBs.
