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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | De Bonis, Maria Luigia Serrano, Manuel Palacios, Jose A. Velasco, Susana Blasco, Maria A. Herranz, Daniel |
| Description | Author Affiliation: Palacios JA ( Telomeres and Telomerase Group, Spanish National Cancer Centre, Madrid E-28029, Spain.) |
| Abstract | Yeast Sir2 deacetylase is a component of the silent information regulator (SIR) complex encompassing Sir2/Sir3/Sir4. Sir2 is recruited to telomeres through Rap1, and this complex spreads into subtelomeric DNA via histone deacetylation. However, potential functions at telomeres for SIRT1, the mammalian orthologue of yeast Sir2, are less clear. We studied both loss of function (SIRT1 deficient) and gain of function $(SIRT1^{super})$ mouse models. Our results indicate that SIRT1 is a positive regulator of telomere length in vivo and attenuates telomere shortening associated with aging, an effect dependent on telomerase activity. Using chromatin immunoprecipitation assays, we find that SIRT1 interacts with telomeric repeats in vivo. In addition, SIRT1 overexpression increases homologous recombination throughout the entire genome, including telomeres, centromeres, and chromosome arms. These findings link SIRT1 to telomere biology and global DNA repair and provide new mechanistic explanations for the known functions of SIRT1 in protection from DNA damage and some age-associated pathologies. |
| ISSN | 00219525 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 7 |
| Volume Number | 191 |
| Language | English |
| Publisher | Rockefeller University Press (United States) |
| Publisher Date | 2010-12-27 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Recombination, Genetic Genetics Sirtuin 1 Telomere Metabolism Acetylation Aging Animals Centromere Chromosome Fragility Chromosomes DNA Damage DNA Methylation Embryo, Mammalian Cytology Fibroblasts Gene Expression Histone Deacetylases Histones Induced Pluripotent Stem Cells Kidney Liver Mice Mice, 129 Strain Mice, Inbred C57BL Mice, Knockout Protein Binding RNA Sister Chromatid Exchange Telomerase Research Support, Non-U.S. Gov't Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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