Nampt is involved in DNA double-strand break repair  

作　　者：Bingtao Zhu Xiaoli Deng Yifan Sun Lin Bai Zhikai Xiahou Yusheng Cong Xingzhi 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》2012年第8期392-398,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.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 

分 类 号：Q691[生物学—生物物理学] TQ172.632[化学工程—水泥工业]