Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 66, Issue 19, Pages 3219-3234Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-009-0105-4
Keywords
Poly(ADP-ribosyl)ation; Acetylation; Genome integrity; Chromatin modifications; Sirtuins
Categories
Funding
- Centre National de la Recherche Scientifique
- Universite de Strasbourg
- Agence Nationale de la Recherche and Ligue Nationale Contre le Cancer
- Comite du Bas-Rhin
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Poly(ADP-ribose) polymerase-1 (Parp-1) and the protein deacetylase SirT1 are two of the most effective NAD(+)-consuming enzymes in the cell with key functions in genome integrity and chromatin-based pathways. Here, we examined the in vivo crosstalk between both proteins. We observed that the double disruption of both genes in mice tends to increase late post-natal lethality before weaning consistent with important roles of both proteins in genome integrity during mouse development. We identified increased spontaneous telomeric abnormalities associated with decreased cell growth in the absence of either SirT1 or SirT1 and Parp-1 in mouse cells. In contrast, the additional disruption of Parp-1 rescued the abnormal pericentric heterochromatin, the nucleolar disorganization and the mitotic defects observed in SirT1-deficient cells. Together, these findings are in favor of key functions of both proteins in cellular response to DNA damage and in the modulation of histone modifications associated with constitutive heterochromatin integrity.
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