Abstract Since the discovery of a yeast gene silencing modifier (Silent Information Modifier 2, SIR2) and its role in maintaining genomic stability more than two decades ago, SIR2 homologs (sirtuins) were identified in diverse species. Sirtuins are protein deacetylases that play diverse roles in proper cellular metabolism including cell cycle progression and maintenance of genomic stability. In yeast, SIR2 interacts with replication origins and protein complexes that affect both replication origin usage and gene silencing. In metazoans, the largest SIR2 homolog, SIRT1, is implicated in epigenetic modifications, circadian signaling, DNA recombination and DNA repair. Until recently, very few studies investigated the role of mammalian SIRT1 in modulating DNA replication. We discuss a newly characterized interaction between human SIRT1 and the DNA replication machinery, reviewing data from recent studies that have investigated how complex signaling pathways that involve SIRT1 affect cellular growth regulatory circuits.

中文翻译：

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额外观点：Sirt1 作为复制启动的守门人以保持基因组稳定性。

摘要 自从二十多年前发现酵母基因沉默修饰剂（Silent Information Modifier 2，SIR2）及其在维持基因组稳定性方面的作用以来，在不同物种中鉴定了 SIR2 同源物（sirtuins）。Sirtuins 是蛋白质脱乙酰酶，在正常的细胞代谢中发挥多种作用，包括细胞周期进程和基因组稳定性的维持。在酵母中，SIR2 与影响复制起点使用和基因沉默的复制起点和蛋白质复合物相互作用。在后生动物中，最大的 SIR2 同系物 SIRT1 与表观遗传修饰、昼夜节律信号、DNA 重组和 DNA 修复有关。直到最近，很少有研究调查哺乳动物 SIRT1 在调节 DNA 复制中的作用。