title: The involvement of c-Myc in the DNA double-strand break repair via regulating radiation-induced phosphorylation of ATM and DNA-PKcs activity.
abstract: Deregulation of c-Myc often occurs in various human cancers, which not only contributes to the genesis and progression of cancers but also affects the outcomes of cancer radio- or chemotherapy. In this study, we have investigated the function of c-Myc in the repair of DNA double-strand break (DSB) induced by γ-ray irradiation. A c-Myc-silenced Hela-630 cell line was generated from HeLa cells using RNA interference technology. The DNA DSBs were detected by γ-H2AX foci, neutral comet assay and pulsed-field gel electrophoresis. We found that the capability of DNA DSB repair in Hela-630 cells was significantly reduced, and the repair kinetics of DSB was delayed as compared to the control Hela-NC cells. Silence of c-myc sensitized the cellular sensitivity to ionizing radiation. The phosphorylated c-Myc (Thr58/pSer62) formed the consistent co-localisation foci with γ-H2AX as well as the phosphorylated DNA-PKcs/S2056 in the irradiated cells. Moreover, depression of c-Myc largely attenuated the ionizing radiation-induced phosphorylation of the ataxia telangiectasia mutated (ATM) and decreased the in vitro kinase activity of DNA-PKcs. Taken together, our results demonstrated that c-Myc protein functions in the process of DNA double-strand break repair, at least partially, through affecting the ATM phosphorylation and DNA-PKcs kinase activity. The overexpression of c-Myc in tumours can account for the radioresistance of some tumour cell types.
authors.affiliation: Department of Radiation Medicine, School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, 215123, China.
authors.forename: Fengmei
authors.initials: F
authors.lastname: Cui
authors.forename: Rong
authors.initials: R
authors.lastname: Fan
authors.forename: Qiu
authors.initials: Q
authors.lastname: Chen
authors.forename: Yongming
authors.initials: Y
authors.lastname: He
authors.forename: Man
authors.initials: M
authors.lastname: Song
authors.forename: Zengfu
authors.initials: Z
authors.lastname: Shang
authors.forename: Shimeng
authors.initials: S
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.forename: Jianping
authors.initials: J
authors.lastname: Cao
authors.forename: Hua
authors.initials: H
authors.lastname: Guan
authors.forename: Ping-Kun
authors.initials: PK
authors.lastname: Zhou
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D051747:DNA-Activated Protein Kinase / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000528:radiation effects*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*
chemical_list: C489427:MYC protein, human; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human