title: Ataxia telangiectasia and Rad3-related overexpressing cancer cells induce prolonged G₂ arrest and develop resistance to ionizing radiation.
abstract: 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.
authors.affiliation: Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Young-Mee
authors.initials: YM
authors.lastname: Kim
authors.forename: Yeo Myoung
authors.initials: YM
authors.lastname: Lee
authors.forename: Soo-Yeon
authors.initials: SY
authors.lastname: Park
authors.forename: Hongryull
authors.initials: H
authors.lastname: Pyo
mesh_terms: D000920:Antibody-Dependent Cell Cytotoxicity / Q000528:radiation effects*; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics*; D000071877:Checkpoint Kinase 1; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D016195:G2 Phase / Q000235:genetics* / Q000528:radiation effects*; D045325:HCT116 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000235:genetics; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics*; D011839:Radiation, Ionizing; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C468783:H2AX protein, human; D006657:Histones; D016159:Tumor Suppressor Protein p53; D011494:Protein Kinases; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; D017346:Protein Serine-Threonine Kinases