| First Author | Mostoslavsky R | Year | 2006 |
| Journal | Cell | Volume | 124 |
| Issue | 2 | Pages | 315-29 |
| PubMed ID | 16439206 | Mgi Jnum | J:112817 |
| Mgi Id | MGI:3663736 | Doi | 10.1016/j.cell.2005.11.044 |
| Citation | Mostoslavsky R, et al. (2006) Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell 124(2):315-29 |
| abstractText | The Sir2 histone deacetylase functions as a chromatin silencer to regulate recombination, genomic stability, and aging in budding yeast. Seven mammalian Sir2 homologs have been identified (SIRT1-SIRT7), and it has been speculated that some may have similar functions to Sir2. Here, we demonstrate that SIRT6 is a nuclear, chromatin-associated protein that promotes resistance to DNA damage and suppresses genomic instability in mouse cells, in association with a role in base excision repair (BER). SIRT6-deficient mice are small and at 2-3 weeks of age develop abnormalities that include profound lymphopenia, loss of subcutaneous fat, lordokyphosis, and severe metabolic defects, eventually dying at about 4 weeks. We conclude that one function of SIRT6 is to promote normal DNA repair, and that SIRT6 loss leads to abnormalities in mice that overlap with aging-associated degenerative processes. |
