Nampt is involved in DNA double-strand break repair

查看全文 作　　者：Bingtao [1]Zhu;Xiaoli [2]Deng;Yifan [1]Sun;Lin [2]Bai;Zhikai [1]Xiahou;Yusheng [2]Cong;Xingzhi [1]Xu

机构地区：[1]Beijing Key Laboratory of DNA Damage Response,College of Life Science,Capital Normal University,Beijing 100048,P.R.China;[2]Institute of Aging Research,Hangzhou Normal University School of Medicine,Hangzhou,Zhejiang 310036,P.R.China

出　　处：《Chinese Journal of Cancer》索引2012年第31卷第8期,共7页

基　　金：was supported by the National Natural Science Foundation of China (No.31130017, 31071190, and 30711120570);the 973 project 2010CB911904;Funding Project for Academic Human Resources Development in Institutions of Higher Learning Under the Jurisdiction of Beijing Municipality (No. PHR20110508) to XX;the 973 project 2012CB911203 to YSC 摘　　要：DNA double-strand break(DSB) is the most severe form of DNA damage,which is repaired mainly through high-fidelity homologous recombination(HR) or error-prone non-homologous end joining(NHEJ).Defects in the DNA damage response lead to genomic instability and ultimately predispose organs to cancer.Nicotinamide phosphoribosyltransferase(Nampt),which is involved in nicotinamide adenine dinucleotide metabolism,is overexpressed in a variety of tumors.In this report,we found that Nampt physically associated with CtIP and DNA-PKcs/Ku80,which are key factors in HR and NHEJ,respectively.Depletion of Nampt by small interfering RNA(siRNA) led to defective NHEJ-mediated DSB repair and enhanced HR-mediated repair.Furthermore,the inhibition of Nampt expression promoted proliferation of cancer cells and normal human fibroblasts and decreased β-galactosidase staining,indicating a delay in the onset of cellular senescence in normal human fibroblasts.Taken together,our results suggest that Nampt is a suppressor of HR-mediated DSB repair and an enhancer of NHEJ-mediated DSB repair,contributing to the acceleration of cellular senescence. 关键词：DNA双链断裂断裂修复人成纤维细胞小分子干扰RNA 非同源末端连接 DNA损伤细胞衰老 siRNA

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Nampt is involved in DNA double-strand break repair

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