Abstract
Much of molecular and cellular responses to DNA double strand breaks (DSBs) have been revealed in irradiated interphase cells. However, it is a question if these responses are also applicable to irradiated mitotic cells, which are totally different from interphase cells in terms of cell morphology, disappearance of nuclear membrane and chromosome condensation. The aim of this study is to elucidate responses of mitotic cells to irradiation.
Upon X irradiation of 0.25~6Gy, phospho-ATM, phospho-H2AX and 53BP1 foci were formed in interphase cells. On the contrary, only phospho-H2AX foci were observed on irradiated mitotic chromosomes. Furthermore, only phospho-H2AX foci were observed on unirradiated mitotic chromosomes. When the irradiated mitotic chromosomes decondense in G1-phase, phospho-ATM, phospho-H2AX and 53BP1 all formed foci, which co-localised perfectly.
These results suggest that higher order chromatin structure may contribute to the different responses between irradiated interphase and mitotic cells. Upon a DSB formation on a highly condensed chromosome, non-chromatin constituting factors such as ATM and 53BP1 may not have access to the aberration site. However, phospho-histone H2AX, one of the chromatin constituting factors, may be able to form foci even on the highly condensed chromosome.
