caa a22 4500 606236333 CHVBK 20210128101247.0 cr unu---uuuuu 210128e20150801xx s 000 0 eng 10.1007/s11010-015-2422-2 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2422-2 The involvement of c-Myc in the DNA double-strand break repair via regulating radiation-induced phosphorylation of ATM and DNA-PKcs activity [Elektronische Daten] [Fengmei Cui, Rong Fan, Qiu Chen, Yongming He, Man Song, Zengfu Shang, Shimeng Zhang, Wei Zhu, Jianping Cao, Hua Guan, Ping-Kun Zhou] 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. Springer Science+Business Media New York, 2015 c-Myc nationallicence DNA-PKcs nationallicence ATM nationallicence DNA double-strand break repair nationallicence Radioresistance nationallicence Cui Fengmei Department of Radiation Medicine, School of Radiation Medicine and Protection, Medical College of Soochow University, 215123, Suzhou, China aut Fan Rong Department of Biochemistry and Molecular, Logistics University of People's Armed Police Force, 300309, Tianjin, China aut Chen Qiu Department of Radiation Medicine, School of Radiation Medicine and Protection, Medical College of Soochow University, 215123, Suzhou, China aut He Yongming Department of Cardiology, The First Affiliated Hospital of Soochow University, 215123, Suzhou, China aut Song Man Department of Radiation Medicine, School of Radiation Medicine and Protection, Medical College of Soochow University, 215123, Suzhou, China aut Shang Zengfu Department of Radiation Medicine, School of Radiation Medicine and Protection, Medical College of Soochow University, 215123, Suzhou, China aut Zhang Shimeng Department of Radiation Toxicology and Oncology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, 100850, Beijing, China aut Zhu Wei Department of Radiation Medicine, School of Radiation Medicine and Protection, Medical College of Soochow University, 215123, Suzhou, China aut Cao Jianping Department of Radiation Medicine, School of Radiation Medicine and Protection, Medical College of Soochow University, 215123, Suzhou, China aut Guan Hua Department of Radiation Toxicology and Oncology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, 100850, Beijing, China aut Zhou Ping-Kun Department of Radiation Medicine, School of Radiation Medicine and Protection, Medical College of Soochow University, 215123, Suzhou, China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 406/1-2(2015-08-01), 43-51 0300-8177 406:1-2<43 2015 406 11010 https://doi.org/10.1007/s11010-015-2422-2 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2422-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Cui Fengmei Department of Radiation Medicine, School of Radiation Medicine and Protection, Medical College of Soochow University, 215123, Suzhou, China aut NATIONALLICENCE 700 1- Fan Rong Department of Biochemistry and Molecular, Logistics University of People's Armed Police Force, 300309, Tianjin, China aut NATIONALLICENCE 700 1- Chen Qiu Department of Radiation Medicine, School of Radiation Medicine and Protection, Medical College of Soochow University, 215123, Suzhou, China aut NATIONALLICENCE 700 1- He Yongming Department of Cardiology, The First Affiliated Hospital of Soochow University, 215123, Suzhou, China aut NATIONALLICENCE 700 1- Song Man Department of Radiation Medicine, School of Radiation Medicine and Protection, Medical College of Soochow University, 215123, Suzhou, China aut NATIONALLICENCE 700 1- Shang Zengfu Department of Radiation Medicine, School of Radiation Medicine and Protection, Medical College of Soochow University, 215123, Suzhou, China aut NATIONALLICENCE 700 1- Zhang Shimeng Department of Radiation Toxicology and Oncology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, 100850, Beijing, China aut NATIONALLICENCE 700 1- Zhu Wei Department of Radiation Medicine, School of Radiation Medicine and Protection, Medical College of Soochow University, 215123, Suzhou, China aut NATIONALLICENCE 700 1- Cao Jianping Department of Radiation Medicine, School of Radiation Medicine and Protection, Medical College of Soochow University, 215123, Suzhou, China aut NATIONALLICENCE 700 1- Guan Hua Department of Radiation Toxicology and Oncology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, 100850, Beijing, China aut NATIONALLICENCE 700 1- Zhou Ping-Kun Department of Radiation Medicine, School of Radiation Medicine and Protection, Medical College of Soochow University, 215123, Suzhou, China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 406/1-2(2015-08-01), 43-51 0300-8177 406:1-2<43 2015 406 11010