Nampt is involved in DNA double-strand break repair / 癌症
Chinese Journal of Cancer
; (12): 392-398, 2012.
Article
Dans En
| WPRIM
| ID: wpr-295868
Responsable en Bibliothèque :
WPRO
ABSTRACT
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.
Texte intégral:
1
Indice:
WPRIM
Sujet Principal:
Physiologie
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Protéines nucléaires
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Cellules HeLa
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Protéines de transport
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Lignée cellulaire
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Vieillissement de la cellule
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Beta-Galactosidase
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Biologie cellulaire
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Antigènes nucléaires
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Petit ARN interférent
Limites du sujet:
Humans
langue:
En
Texte intégral:
Chinese Journal of Cancer
Année:
2012
Type:
Article