Van Meter Michael, Mao Zhiyong, Gorbunova Vera, Seluanov Andrei
Department of Biology, University of Rochester, Rochester, NY 14627, USA.
Aging (Albany NY). 2011 Sep;3(9):829-35. doi: 10.18632/aging.100389.
The sirtuin gene family comprises an evolutionarily ancient set of NAD+ dependent protein deacetylase and mono-ADP ribosyltransferase enzymes. Found in all domains of life, sirtuins regulate a diverse array of biological processes, including DNA repair, gene silencing, apoptosis and metabolism. Studies in multiple model organisms have indicated that sirtuins may also function to extend lifespan and attenuate age-related pathologies. To date, most of these studies have focused on the deacetylase activity of sirtuins, and relatively little is known about the other biochemical activity of sirtuins, mono-ADP ribosylation. We recently reported that the mammalian sirtuin, SIRT6, mono-ADP ribosylates PARP1 to promote DNA repair in response to oxidative stress. In this research perspective we review the role of SIRT6 in DNA repair and discuss the emerging implications for sirtuin directed mono-ADP ribosylation in aging and age-related diseases.
沉默调节蛋白基因家族由一组进化上古老的依赖烟酰胺腺嘌呤二核苷酸（NAD+）的蛋白质脱乙酰酶和单磷酸腺苷核糖基转移酶组成。沉默调节蛋白存在于生命的所有领域，调节各种生物过程，包括DNA修复、基因沉默、细胞凋亡和新陈代谢。对多种模式生物的研究表明，沉默调节蛋白也可能具有延长寿命和减轻与年龄相关疾病的作用。迄今为止，这些研究大多集中在沉默调节蛋白的脱乙酰酶活性上，而对沉默调节蛋白的另一种生化活性——单磷酸腺苷核糖基化，了解相对较少。我们最近报道，哺乳动物沉默调节蛋白SIRT6通过单磷酸腺苷核糖基化聚（ADP-核糖）聚合酶1（PARP1）来促进氧化应激反应中的DNA修复。在本研究展望中，我们综述了SIRT6在DNA修复中的作用，并讨论了沉默调节蛋白介导的单磷酸腺苷核糖基化在衰老及与年龄相关疾病中的新意义。
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