Cohesin's ATPase activity couples cohesin loading onto DNA with Smc3 acetylation.
Cohesin's ATPase activity couples cohesin loading onto DNA with Smc3 acetylation.
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DOI：
10.1016/j.cub.2014.08.011
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发表时间：
2014-10-06
期刊：
影响因子：
--
通讯作者：
Peters JM
中科院分区：
文献类型：
--
作者：
Ladurner R;Bhaskara V;Huis in 't Veld PJ;Davidson IF;Kreidl E;Petzold G;Peters JM
粘着蛋白通过拓扑学地将姐妹DNA分子截留在其环状结构内来介导姐妹染色单体的粘着。粘附素通过Scc 2/NIPBL-Scc 4/MAU 2-加载复合物以依赖于粘附素Smc 1和Smc 3亚基的腺苷三磷酸酶（ATP酶）活性的方式加载到DNA上。随后的凝聚力的建立在DNA复制过程中依赖于Smc 3乙酰化Esco 1和Esco 2和sororin的招聘，它“锁定”的DNA上的凝聚力通过灭活的凝聚力释放因子Wapl。人粘附素ATP酶突变体以依赖于加载复合物的方式与DNA瞬时缔合，但不能通过消耗Wapl而稳定在染色质上。这些突变体不能被乙酰化，不能与sororin相互作用，并且不介导凝聚力。在ATP酶突变体中Smc 3乙酰化的缺乏不是它们与DNA的瞬时结合的结果，而是直接由它们不能水解ATP引起的，因为野生型粘附素的乙酰化也依赖于ATP水解。我们的数据表明，凝聚力的建立涉及以下步骤。首先，粘附素以取决于加载复合物的方式与DNA短暂结合。随后，粘附素的ATP水解导致DNA的截留，并将Smc 3转化为可以乙酰化的状态。最后，Smc 3乙酰化导致sororin的募集、Wapl的抑制和DNA上粘附素的稳定。我们的发现，粘附素的ATP酶活性所需的粘附素加载和Smc 3乙酰化的可能性，凝聚力的建立是直接耦合到反应中，粘附素截留DNA。黏连蛋白最初通过负载复合物与染色质短暂相互作用黏连蛋白的ATP酶活性是动态染色质-黏连蛋白相互作用所必需的Smc 3乙酰化不会显著改变黏连蛋白的ATP酶活性Smc 3乙酰化需要黏连蛋白的ATP酶活性Ladurner et al.目前的证据表明，三磷酸腺苷酶（ATP酶）的活性的cohesin复合物所需的cohesin乙酰化，表明姐妹染色单体截留cohesin耦合到建立的凝聚力。
Cohesin mediates sister chromatid cohesion by topologically entrapping sister DNA molecules inside its ring structure. Cohesin is loaded onto DNA by the Scc2/NIPBL-Scc4/MAU2-loading complex in a manner that depends on the adenosine triphosphatase (ATPase) activity of cohesin’s Smc1 and Smc3 subunits. Subsequent cohesion establishment during DNA replication depends on Smc3 acetylation by Esco1 and Esco2 and on recruitment of sororin, which “locks” cohesin on DNA by inactivating the cohesin release factor Wapl. Human cohesin ATPase mutants associate transiently with DNA in a manner that depends on the loading complex but cannot be stabilized on chromatin by depletion of Wapl. These mutants cannot be acetylated, fail to interact with sororin, and do not mediate cohesion. The absence of Smc3 acetylation in the ATPase mutants is not a consequence of their transient association with DNA but is directly caused by their inability to hydrolyze ATP because acetylation of wild-type cohesin also depends on ATP hydrolysis. Our data indicate that cohesion establishment involves the following steps. First, cohesin transiently associates with DNA in a manner that depends on the loading complex. Subsequently, ATP hydrolysis by cohesin leads to entrapment of DNA and converts Smc3 into a state that can be acetylated. Finally, Smc3 acetylation leads to recruitment of sororin, inhibition of Wapl, and stabilization of cohesin on DNA. Our finding that cohesin’s ATPase activity is required for both cohesin loading and Smc3 acetylation raises the possibility that cohesion establishment is directly coupled to the reaction in which cohesin entraps DNA. Cohesin initially interacts with chromatin transiently via the loading complex Cohesin’s ATPase activity is required for dynamic chromatin-cohesin interactions Smc3 acetylation does not significantly alter cohesin’s ATPase activity Cohesin’s ATPase activity is required for Smc3 acetylation Ladurner et al. present evidence that the adenosine triphosphatase (ATPase) activity of the cohesin complex is required for cohesin acetylation, suggesting that sister-chromatid entrapment by cohesin is coupled to the establishment of cohesion.
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