Ataxia Telangiectasia and Rad3-Related Overexpressing Cancer Cells Induce Prolonged G(2) Arrest and Develop Resistance to Ionizing Radiation

摘要

We investigated whether ataxia telangiectasia and rad3-related (ATR) kinases regulate prolongation of ionizing radiation (IR) induced-G(2) arrest and radioresistance in ataxia telangiectasia mutated-intact cancer cells. ATR overexpressing cancer cells showed prolonged-G(2) arrest after IR exposure and were significantly resistant to DNA damaging stresses. The phosphorylation of p-Ser(15)-p53, p-Ser(345)-Chk1, and p-Tyr(15)-Cdk1 phosphorylation was increased until 36 h after IR exposure in ATR-overexpressing cells, whereas p-Ser(10)-histone H3 decreased. ATR-overexpressing cells also showed rapid attenuation of increased gamma-H2AX foci after IR exposure compared with control cells. In contrast, ATR knockdown cells had limited clearance of gamma-H2AX foci after IR exposure. In conclusion, ATR overexpression seems to primarily induce prolonged G(2) arrest after IR exposure, which increases IR resistance by enhancing DNA damage repair. These results may provide useful clues for understanding the function of ATR in controlling IR-induced G(2) arrest and radiation response.