The involvement of c-Myc in the DNA double-strand break repair via regulating radiation-induced phosphorylation of ATM and DNA-PKcs activity.
Mol Cell Biochem
; 406(1-2): 43-51, 2015 Aug.
Article
em En
| MEDLINE
| ID: mdl-26049366
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
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Processamento de Proteína Pós-Traducional
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Proteínas Proto-Oncogênicas c-myc
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Reparo do DNA
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Proteína Quinase Ativada por DNA
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Proteínas Mutadas de Ataxia Telangiectasia
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article