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

Cell Cycle. 2006 Apr;5(8):873-7. doi: 10.4161/cc.5.8.2690. Epub 2006 Apr 17.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Inducing Factor / physiology*
  • Cell Death
  • Cell Line
  • DNA Damage*
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation*
  • Humans
  • Mice
  • Models, Biological
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / metabolism
  • Poly(ADP-ribose) Polymerases / physiology*
  • Resveratrol
  • Sirtuin 1
  • Sirtuins / physiology*
  • Stilbenes / pharmacology


  • Apoptosis Inducing Factor
  • Enzyme Inhibitors
  • Stilbenes
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • SIRT1 protein, human
  • Sirtuin 1
  • Sirtuins
  • Resveratrol