Nampt is involved in DNA double-strand break repair.
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.
Beijing Key Laboratory of DNA Damage Response, College of Life Science, Capital Normal University, Beijing 100048, P. R. China.
Bingtao
B
Zhu
Xiaoli
X
Deng
Yifan
Y
Sun
Lin
L
Bai
Zhikai
Z
Xiahou
Yusheng
Y
Cong
Xingzhi
X
Xu
D000936:Antigen-Antibody Complex / Q000378:metabolism; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D016922:Cellular Senescence; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair; D004260:DNA Repair; D051747:DNA-Activated Protein Kinase / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004706:Endodeoxyribonucleases; D005347:Fibroblasts / Q000166:cytology; D006367:HeLa Cells; D059765:Homologous Recombination / Q000235:genetics / Q000502:physiology; D006801:Humans; D000072200:Ku Autoantigen; D054409:Nicotinamide Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D001616:beta-Galactosidase / Q000378:metabolism
D000936:Antigen-Antibody Complex; D034961:Antigens, Nuclear; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D054409:Nicotinamide Phosphoribosyltransferase; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D004706:Endodeoxyribonucleases; C410741:RBBP8 protein, human; D001616:beta-Galactosidase; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen