Functional interplay between Parp-1 and SirT1 in genome integrity and chromatin-based processes |
| |
Authors: | Rosy El Ramy Najat Magroun Nadia Messadecq Laurent R Gauthier François D Boussin Ullas Kolthur-Seetharam Valérie Schreiber Michael W McBurney Paolo Sassone-Corsi Françoise Dantzer |
| |
Institution: | (1) IREBS-FRE3211, ESBS, Bld S. Brant, BP10413, 67412 Illkirch, France;(2) IGBMC, 67404 Illkirch, France;(3) Laboratoire de Radiopathologie, CEA, IRCM-INSERM U967, 92265 Fontenay-aux-Roses, France;(4) Department of Biological Sciences, Tata Institute of Fundamental Research, Colaba, Mumbai, 400005, India;(5) Center for Cancer Therapeutics, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON, Canada;(6) Department of Pharmacology, University of California, GNRF, Irvine, CA 92697, USA |
| |
Abstract: | 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. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|