期刊
CELL CYCLE
卷 5, 期 8, 页码 873-877出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.5.8.2690
关键词
PARP; SIRT1; DNA damage; NAD; cell death; AIF
类别
Cell survival after genotoxic stress is determined by a counterbalance of pro- and anti-death factors. Sirtuins (SIRTs) are deacetylases that promote cell survival whereas poly(ADP-ribose) polymerases (PARPs) can act both as survival and death inducing factor and the two protein families are strictly dependent on NAD+ for their activities. Here we report that SIRT1 modulates PARP-1 activity upon DNA damage. Activation of SIRT1 by resveratrol leads to reduced PARP-1 activity and there is a drastic increase in PAR synthesis in sirt1-null cells. The unbalanced regulation of PARP-1 in the absence of SIRT1 results in AIF ( apoptosis inducing factor)-mediated cell death. Our findings establish a functional link between the two NAD(+)-dependent enzyme systems and provide a physiological interpretation for the mechanism of death in cells lacking SIRT1.
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