Genomic instability and aging-like phenotype in the absence of mammalian SIRT6.
Document Type
Article
Publication Date
2006
Keywords
Animals, Antigens-CD30, Cell-Proliferation, Chromatin, DNA-Damage, DNA-Repair, Genetic-Diseases-Inborn, Genomic-Instability, Humans, Lymphocytes, Mice, Mice-Knockout, Phenotype, Radiation-Tolerance, Research-Support-N, I, H, -Extramural, Research-Support-Non-U, S, -Gov't, Signal-Transduction, Sirtuins
First Page
315
Last Page
329
JAX Source
Cell 2006 Jan; 124(2):315-29.
Abstract
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.
Recommended Citation
Mostoslavsky R,
Chua KF,
Lombard DB,
Pang WW,
Fischer MR,
Gellon L,
Liu P,
Nunez N,
Bronson R,
Frendewey D,
et a.
Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell 2006 Jan; 124(2):315-29.