中文摘要：

目的探讨Tip60对细胞辐射敏感性的影响及相关机制。方法采用siRNA和Tip60乙酰转移酶抑制剂漆树酸，抑制U20S细胞中Tip60的表达或乙酰转移酶活性；用克隆形成率分析细胞对^60Coγ射线的敏感性；采用7-H2AX原位免疫荧光集簇点法，检测DNA双链断裂损伤修复；用免疫共沉淀检测蛋白质的相互作用。结果siRNA沉默Tip60表达明显提高了U20S细胞对1、2Gy中、低剂量1射线的敏感性（t=3．364、3．979，P〈0．05），但对4Gy大剂量照射的细胞存活率无明显影响。γ-H2AX集簇点检测结果表明，照射后1、4和8h，Tip60失活导致细胞DNA双链断裂修复能力降低（t=3．875、3．183和3．175，P〈0．05）。细胞在受到电离辐射损伤后，Tip60与DNA修复蛋白DNA-PKcs发生相互作用，漆树酸能抑制DNA-PKcs的T2609位点的磷酸化。结论Tip60通过与DNA—PKcs相互作用，调控细胞DNA双链断裂修复机制，对细胞辐射敏感性产生影响。

英文摘要：

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 Tip60 plays 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.