Abstract
Ionizing radiation induces DNA double-strand breaks, which are the major cause of the detrimental effects of radiation. They activate a checkpoint protein, ATM, and it phosphorylates a variety of proteins to exert its functions. Histone H2AX, a member of the histone H2A family, is phosphorylated immediately after irradiation, and phosphorylated H2AX forms discrete foci. Because the number of foci corresponds to the number of DNA double strand breaks, it has generally been thought that the phosphorylation of H2AX is caused by DNA double strand breaks. Present study reveals phosphorylated histone H2AX foci on mitotic cells irradiated with X-rays. As expected, phosphorylated H2AX foci were found at the ends of chromosome fragments in metaphase cells. In addition, the foci were detected on chromosomal bridges between two sister nuclei in anaphase. Furthermore, we found duplicated phosphorylated H2AX foci exactly at the same sites on both sister chromatids 20 hours after irradiation. These results indicate that a change in higher-order chromatin structure, caused by DNA double-strand breaks, is involved in the phosphorylation of histone H2AX. [J Radiat Res 44:412 (2003)]
