Esco1 Acetylates Cohesin via a Mechanism Different from That of Esco2
Esco1 Acetylates Cohesin via a Mechanism Different from That of Esco2
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DOI：
10.1016/j.cub.2015.05.017
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发表时间：
2015-06-29
期刊：
影响因子：
9.2
通讯作者：
Shirahige, Katsuhiko
中科院分区：
文献类型：
--
作者：
Minamino, Masashi;Ishibashi, Mai;Shirahige, Katsuhiko
姐妹染色单体凝聚是由凝聚素介导的，它对染色体的精确分离是必不可少的。粘附素亚基SMC 1、SMC 3和Rad 21形成一个三环，其中姐妹染色单体被认为被捕获。这一事件需要SMC 3的乙酰化以及乙酰转移酶Esco 1和Esco 2将sororin与cohesin结合在一起，但这些乙酰转移酶的功能机制仍然难以捉摸。在这里，我们发现，Esco 1需要Pds 5，一个结合到Rad 21的粘附素调节亚基，通过SMC 3乙酰化和sororin的染色质缔合的稳定形成凝聚力，而Esco 2功能不受Pds 5耗尽的影响。与Esco 1和Pds 5之间的功能联系一致，Pds 5仅与Esco 1相互作用，并且这种相互作用依赖于独特且保守的Esco 1结构域。至关重要的是，这种相互作用是必要的SMC 3乙酰化和姐妹染色单体凝聚力。Esco 1在整个间期以Esco 1-Pds 5相互作用的方式定位于染色体上的粘附素定位位点，并且在DNA复制前后可以乙酰化SMC 3。这些结果表明，Esco 1通过与Esco 2不同的机制乙酰化SMC 3。我们提出，通过与Esco 1的一个独特的结构域相互作用，Pds 5招募Esco 1染色质结合的粘附素复合物形成凝聚力。此外，Esco 1乙酰化SMC 3独立于DNA复制。
Sister chromatid cohesion is mediated by cohesin and is essential for accurate chromosome segregation. The cohesin subunits SMC1, SMC3, and Rad21 form a tripartite ring within which sister chromatids are thought to be entrapped. This event requires the acetylation of SMC3 and the association of sororin with cohesin by the acetyltransferases Esco1 and Esco2 in humans, but the functional mechanisms of these acetyltransferases remain elusive. Here, we showed that Esco1 requires Pds5, a cohesin regulatory subunit bound to Rad21, to form cohesion via SMC3 acetylation and the stabilization of the chromatin association of sororin, whereas Esco2 function was not affected by Pds5 depletion. Consistent with the functional link between Esco1 and Pds5, Pds5 interacted exclusively with Esco1, and this interaction was dependent on a unique and conserved Esco1 domain. Crucially, this interaction was essential for SMC3 acetylation and sister chromatid cohesion. Esco1 localized to cohesin localization sites on chromosomes throughout interphase in a manner that required the Esco1-Pds5 interaction, and it could acetylate SMC3 before and after DNA replication. These results indicate that Esco1 acetylates SMC3 via a mechanism different from that of Esco2. We propose that, by interacting with a unique domain of Esco1, Pds5 recruits Esco1 to chromatin-bound cohesin complexes to form cohesion. Furthermore, Esco1 acetylates SMC3 independently of DNA replication.