Control of AIF-mediated cell death by the functional interplay of SIRT1 and PARP-1 in response to DNA damage - Archive ouverte HAL Access content directly
Journal Articles Cell Cycle Year : 2006

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

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.

Dates and versions

hal-04094344 , version 1 (10-05-2023)

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Ullas Kolthur Seetharam, Françoise Dantzer, Michael W. Mcburney, Gilbert de Murcia, Paolo Sassone-Corsi. Control of AIF-mediated cell death by the functional interplay of SIRT1 and PARP-1 in response to DNA damage. Cell Cycle, 2006, 5 (8), pp.873-877. ⟨10.4161/cc.5.8.2690⟩. ⟨hal-04094344⟩
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