Host: The Japan Radiation Research Society
When cells were exposed to ionizing irradiation, the cells were arrested and do not enter in mitosis. Otherwise, cells carrying unrepaired or misrepaired DNA damages might be lethal or prone to cancer. Recently accumulating evidences have been supported that DNA-PK and ATM play an important role in this mechanism, but it is still unclear how these proteins works cooperate. Using the ATM mutated cells AT5BISV and LY 294002, a specific inhibitor of DNA-PK, we investigated the role of DNA-PK and ATM in radiohypersensitivity and control of cell cycle check point following irradiation. Colony Surviving assay showed that 50 uM of LY294002 made AT5 cells 2 order hypersensitive to irradiation. AT5 cells in G2/M phase were accumulated of 60% of total, but more than 10% cells were escaped from G2 and reached in mitosis. The mitotic chromosomes of AT5 were quite badly damaged, whilst those of control cells were almost repaired. These findings suggested that DNA-PK and ATM cooperatively control DNA repair machinery and cell cycle check point regulation, particularly G2-M transition control. [J Radiat Res 44:410 (2003)]
