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Cell Cycle. 2006 Apr;5(8):873-7. Epub 2006 Apr 17.

Control of AIF-mediated cell death by the functional interplay of SIRT1 and PARP-1 in response to DNA damage.

Author information

1
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, Inserm, Université Louis Pasteur, Strasbourg, France.

Abstract

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.

PMID:
16628003
DOI:
10.4161/cc.5.8.2690
[Indexed for MEDLINE]

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