Ataxia telangiectasia and Rad3-related overexpressing cancer cells induce prolonged G₂ arrest and develop resistance to ionizing radiation.

We investigated whether ataxia telangiectasia and rad3-related (ATR) kinases regulate prolongation of ionizing radiation (IR) induced-G₂ arrest and radioresistance in ataxia telangiectasia mutated-intact cancer cells. ATR overexpressing cancer cells showed prolonged-G₂ arrest after IR exposure and were significantly resistant to DNA damaging stresses. The phosphorylation of p-Ser¹⁵-p53, p-Ser³⁴⁵-Chk1, and p-Tyr¹⁵-Cdk1 phosphorylation was increased until 36 h after IR exposure in ATR-overexpressing cells, whereas p-Ser¹⁰-histone H3 decreased. ATR-overexpressing cells also showed rapid attenuation of increased γ-H2AX foci after IR exposure compared with control cells. In contrast, ATR knockdown cells had limited clearance of γ-H2AX foci after IR exposure. In conclusion, ATR overexpression seems to primarily induce prolonged G₂ 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 G₂ arrest and radiation response.