Deficiency of DNA double-strand break repair and enhanced radiosensitivity in Tip60 silenced cells
10.3760/cma.j.issn.0254-5098.2011.05.001
- VernacularTitle:Tip60基因沉默对细胞DNA双链断裂修复和辐射敏感性的影响
- Author:
Rong FAN
;
Shimeng ZHANG
;
Xiaodan LIU
;
Yu WANG
;
Qinzhi XU
;
Pingkun ZHOU
- Publication Type:Journal Article
- Keywords:
Tip60;
DNA-PKcs;
Radiosensitivity;
DNA double-strand break;
DNA repair
- From:
Chinese Journal of Radiological Medicine and Protection
2011;31(5):511-514
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of Tip60 on the cellular radiosensitivity,and to explore the related mechanism.Methods siRNA and anacardic acid (AA,an inhibitor of Tip60 acetyltransferase) were used to inhibit Tip60 expression and its acetyltransferase activity,respectively.Radiosensitivity was analyzed by colony-forming ability assay.γ-H2AX foci were detected to analyze the DNA double-strand break (DSB).Immunoprecipitation was used to determine the interaction of proteins.Results siRNA-mediated silencing of Tip60 led to enhanced sensitivity of U2OS cells at 1,2 Gy after γ-ray irradiation,but had no significant effect at 4 Gy post-irradiation ( t =3.364,3.979,P ＜ 0.05 ).γ-H2AX foci detection indicated that Tip60 silencing resulted in a decreased capability of DNA doublestrand break repair at 1,4 and 8 h after irradiation( t =3.875,3.183 and 3.175,respectively,P ＜ 0.05 ).The interaction of Tip60 and DNA-PKcs was prompted by ionizing radiation.Anacardic acid largely abrogated the phosphorylation of DNA-PKcs at T2609 site induced by irradiation.Conclusions Tip60plays a role in the cellular response to ionizing radiation-induced DNA damage through,at least in part,interacting with DNA-PKcs and regulating its phosphorylation.
