Human SIRT1 associates with mitotic chromatin and contributes to chromosomal condensation
Human SIRT1 associates with mitotic chromatin and contributes to chromosomal condensation
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DOI：
10.4161/cc.10.14.15913
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发表时间：
2011-07-15
期刊：
影响因子：
4.3
通讯作者：
Okorokov, Andrei L.
中科院分区：
文献类型：
--
作者：
Fatoba, Samuel T.;Okorokov, Andrei L.
SIRT1是一种nad依赖性去乙酰化酶，参与基因表达、代谢、基因组稳定性和抗衰老的细胞控制。在这里，我们报道SIRT1水平在中期上升，导致SIRT1与有丝分裂染色质的整体关联直到末期。此外，SIRT1通过介导组蛋白H1和凝缩蛋白I复合物的染色体负载来促进染色体凝聚。SIRT1敲低导致不适当的凝聚和整体异常的有丝分裂。我们的数据突出了SIRT1在有丝分裂中维持染色体稳定性中的新作用，并表明SIRT1活性在衰老和肿瘤发生过程中的降低可能导致非整倍体和基因组不稳定。
SIRT1 is a NAD-dependent deacetylase that participates in cellular controls of gene expression, metabolism, genomic stability and anti-aging. Here we report that SIRT1 levels rise in prometaphase leading to SIRT1 global association with mitotic chromatin until telophase. Moreover, SIRT1 contributes to chromosomal condensation by mediating chromosomal loading of histone H1 and the condensin I complex. Consistently, SIRT1 knockdown led to improper condensation and overall aberrant mitosis. Our data highlight new role for SIRT1 in maintenance of chromosome stability in mitosis and suggests how diminished SIRT1 activity during aging and tumorigenesis may lead to aneuploidy and genomic instability.