Cell · 2006
Genomic instability and aging-like phenotype in the absence of mammalian SIRT6.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
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История · было → стало
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Mostoslavsky Raul, Chua Katrin F, Lombard David B, Pang Wendy W, Fischer Miriam R, Gellon Lionel, Liu Pingfang, Mostoslavsky Gustavo, Franco Sonia, Murphy Michael M, Mills Kevin D, Patel Parin, Hsu Joyce T, Hong Andrew L, Ford Ethan, Cheng Hwei-Ling, Kennedy Caitlin, Nunez Nomeli, Bronson Roderick, Frendewey David, Auerbach Wojtek, Valenzuela David, Karow Margaret, Hottiger Michael O, Hursting Stephen, Barrett J Carl, Guarente Leonard, Mulligan Richard, Demple Bruce, Yancopoulos George D, Alt Frederick W
Аннотация
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.