Acetylation of Smc3 by Eco1 is required for S phase sister chromatid cohesion in both human and yeast
Acetylation of Smc3 by Eco1 is required for S phase sister chromatid cohesion in both human and yeast
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DOI：
10.1016/j.molcel.2008.06.006
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发表时间：
2008-07-11
期刊：
影响因子：
16
通讯作者：
Qin, Jun
中科院分区：
文献类型：
--
作者：
Zhang, Jinglan;Shi, Xiaomin;Qin, Jun
姐妹染色单体凝聚通常在S期建立，该过程依赖于凝聚建立因子Ecol，一种保守的乙酰转移酶。然而，由于缺乏已知的体内底物，Ecol如何调节凝聚力尚不清楚。在这里，我们报告说，酵母Ecol和它的人类直系同源物，ESCO 1，都乙酰化Smc 3，一个组成部分的粘连蛋白复合物，物理上举行的姐妹染色单体在一起，在两个保守的赖氨酸残基。将这些赖氨酸残基突变为不可乙酰化的形式导致酵母和人类中姐妹染色单体凝聚力和基因组不稳定性的损失增加。此外，我们阐明了Ecol的乙酰转移酶活性对其功能至关重要。因此，我们的研究确定了乙酰转移酶Ecol的分子靶点，并揭示了Smc 3乙酰化是调节姐妹染色单体凝聚力的保守机制。
Sister chromatid cohesion is normally established in S phase in a process that depends on the cohesion establishment factor Ecol, a conserved acetyltransferase. However, due to the lack of known in vivo substrates, how Ecol regulates cohesion is not understood. Here we report that yeast Ecol and its human ortholog, ESCO1, both acetylate Smc3, a component of the cohesin complex that physically holds the sister chromatid together, at two conserved lysine residues. Mutating these lysine residues to a nonacetylatable form leads to increased loss of sister chromatid cohesion and genome instability in both yeast and human. In addition, we clarified that the acetyltransferase activity of Ecol is essential for its function. Our study thus identified a molecular target for the acetyltransferase Ecol and revealed that Smc3 acetylation is a conserved mechanism in regulating sister chromatid cohesion.