Hos1 Is a Lysine Deacetylase for the Smc3 Subunit of Cohesin
Hos1 Is a Lysine Deacetylase for the Smc3 Subunit of Cohesin
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DOI：
10.1016/j.cub.2010.08.019
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发表时间：
2010-09
期刊：
影响因子：
9.2
通讯作者：
Bo Xiong;Shuai Lu;J. Gerton
中科院分区：
文献类型：
--
作者：
Bo Xiong;Shuai Lu;J. Gerton
染色体内聚是一个细胞周期调节的过程，在这个过程中，姐妹染色单体从复制开始一直保持在一起，直到在中期到后期转变时分离，从而确保染色体的准确分离[1-9]。染色体内聚在S期建立，这一过程需要内聚蛋白复合体的四个亚基（Smc1、Smc3、Mcd1/Scc1和Irr1/Scc3）和乙酰转移酶Eco1的参与[10-13]。Eco1在两个进化上保守的赖氨酸残基上乙酰化Smc3，促进了出芽酵母和人类S期内聚的建立[14-16]。在这里，我们报道Hos1，一个进化上保守的I类组蛋白去乙酰化酶家族的成员，作为Smc3 inS的去乙酰化酶。酵母。我们检测了9株组蛋白去乙酰化酶缺失菌株的Smc3乙酰化水平，发现乙酰化水平在hos1Δ菌株s期后特异性升高。共免疫沉淀实验表明，Hos1与Smc3相互作用，并且在细胞进入后期时相互作用最为明显。我们提供的直接证据表明，Hos1可以脱乙酰化Smc3，并保留脱乙酰化Smc3的可溶性池。在WT和eco1突变株中，过表达Hos1导致Smc3乙酰化减少和内聚缺陷；Hos1活性位点的突变消除了这些缺陷。Hos1可能有助于维持一个可用于新染色体内聚的未乙酰化Smc3库。
Chromosome cohesion is a cell-cycle-regulated process in which sister chromatids are held together from the time of replication until the time of separation at the metaphase-to-anaphase transition, ensuring accurate chromosome segregation [1–9]. Chromosome cohesion is established during S phase, and this process requires the four subunits of the cohesin complex (Smc1, Smc3, Mcd1/Scc1, and Irr1/Scc3) and the acetyltransferase Eco1 [10–13]. Acetylation of Smc3 by Eco1 at two evolutionarily conserved lysine residues promotes cohesion establishment during S phase in budding yeast and humans [14–16]. Here we report that Hos1, a member of the evolutionarily conserved class I histone deacetylase family, acts as a deacetylase for Smc3 inS. cerevisiae. We examine the Smc3 acetylation level in nine histone deacetylase deletion strains and find that the acetylation level is increased specifically in a hos1Δ strain post-S phase. Coimmunoprecipitation experiments show that Hos1 interacts with Smc3 and that the interaction is most pronounced as cells reach anaphase. We provide direct evidence that Hos1 can deacetylate Smc3 and retains a soluble pool of deacetylated Smc3. Overexpression of Hos1 results in less acetylation of Smc3 and cohesion defects in both WT andeco1mutant strains; mutation of the Hos1 active site abolishes the defects. Hos1 may help to maintain a pool of unacetylated Smc3 that can be used for new chromosome cohesion.