1. Control of AIF-mediated cell death by the functional interplay of SIRT1 and PARP-1 in response to DNA damage
- Author
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Ullas Kolthur-Seetharam, Michael W. McBurney, Françoise Dantzer, Gilbert de Murcia, Paolo Sassone-Corsi, Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Cancérogenèse et mutagenèse moléculaire et structurale (CMMS), Centre National de la Recherche Scientifique (CNRS), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Dantzer, Françoise, Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Klotz, Evelyne
- Subjects
MESH: Cell Death ,Poly (ADP-Ribose) Polymerase-1 ,Genotoxic Stress ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,Resveratrol ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Sirtuin 1 ,MESH: Stilbenes ,Stilbenes ,Sirtuins ,MESH: Animals ,Enzyme Inhibitors ,chemistry.chemical_classification ,0303 health sciences ,Cell Death ,food and beverages ,Apoptosis Inducing Factor ,MESH: Sirtuins ,MESH: Gene Expression Regulation ,Cell biology ,MESH: Enzyme Inhibitors ,Apoptosis-inducing factor ,Poly(ADP-ribose) Polymerases ,hormones, hormone substitutes, and hormone antagonists ,Programmed cell death ,DNA damage ,Poly ADP ribose polymerase ,Biology ,Models, Biological ,Cell Line ,03 medical and health sciences ,[SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,Animals ,Humans ,Molecular Biology ,MESH: Mice ,030304 developmental biology ,MESH: DNA Damage ,MESH: Humans ,MESH: Poly(ADP-ribose) Polymerases ,MESH: Models, Biological ,Cell Biology ,MESH: Cell Line ,Enzyme ,MESH: Apoptosis Inducing Factor ,chemistry ,Gene Expression Regulation ,NAD+ kinase ,030217 neurology & neurosurgery ,Developmental Biology ,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.
- Published
- 2006