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Sub-cellular localization, expression and functions of Sirt6 during the cell cycle in HeLa cells.

机译:在HeLa细胞的细胞周期中,Sirt6的亚细胞定位,表达和功能。

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Sirtuin 6 (Sirt6), a mammalian Sir2 (silent information regulator-2) ortholog, is an NAD (+) -dependent histone deacetylase that modulates chromatin structure and genomic stability. Sirt6 knockout cells demonstrate genomic instability, and a deficiency of Sirt6 in mice leads to an aging phenotype early in life. Some nuclear sirtuins, such as Sirt7, localize to the nucleolus, and others, such as Sirt1, are mainly found in the nucleoplasm, with a minor population in the nucleolus. However, Sirt6 has been reported to be a nucleoplasmic protein that is excluded from the nucleolus. Because of the importance of a protein's localization to its interactions and functions, we evaluated Sirt6 sub-cellular localization, expression and functions throughout the cell cycle in HeLa cells. Our results showed that during interphase, Sirt6 was mostly localized to the nucleus, although it was not absent from the nucleolus. Sirt6 was enriched in the nucleolus in the G 1 phase of the cell cycle, while S phase nucleoli were almost entirely free of Sirt6. During mitosis, the Sirt6 expression level was increased, and while Sirt6 was not associated with condensed chromosomes, it partially co-localized with mitotic spindles. Cells overexpressing Sirt6 had a lower proliferation rate with a lower percentage of cells in mitosis. These findings suggest roles for Sirt6 in the nucleolus and in the mitotic phase of the cell cycle.
机译:Sirtuin 6(Sirt6)是哺乳动物Sir2(沉默信息调节剂2)直向同源物,是一种NAD(+)依赖性组蛋白脱乙酰基酶,可调节染色质结构和基因组稳定性。 Sirt6基因敲除细胞显示出基因组不稳定,而Sirt6基因在小鼠体内的缺乏会导致其生命早期的衰老表型。一些核沉默蛋白,如Sirt7,位于核仁中,而其他核沉默蛋白,如Sirt1,则主要存在于核质中,少数在核仁中。但是,据报道Sirt6是一种被排除在核仁之外的核质蛋白。由于蛋白质的定位对其相互作用和功能的重要性,我们在整个HeLa细胞的整个细胞周期中评估了Sirt6亚细胞的定位,表达和功能。我们的结果表明,在相间期,Sirt6大部分位于核内,尽管核仁中不存在。 Sirt6在细胞周期的G 1期富含核仁,而S期核仁几乎完全不含Sirt6。在有丝分裂期间,Sirt6表达水平增加,而Sirt6与浓缩染色体无关,但它与有丝分裂纺锤部分共定位。过表达Sirt6的细胞增殖率较低,有丝分裂中细胞的百分比较低。这些发现提示Sirt6在细胞周期的核仁和有丝分裂期中的作用。

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