Structural Insights into Ring Formation of Cohesin and Related Smc Complexes.
Structural Insights into Ring Formation of Cohesin and Related Smc Complexes.
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DOI：
10.1016/j.tcb.2016.04.002
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发表时间：
2016-09
影响因子：
19
通讯作者：
Löwe J
中科院分区：
文献类型：
--
作者：
Gligoris T;Löwe J
凝聚素通过形成一个环绕DNA的大环结构促进姐妹染色单体的凝聚。它的功能依赖于两种结构维持染色体（Smc）蛋白，这是发现在几乎所有的生物测试，从细菌到人类。Smc复合物，如粘附素、凝聚素、Smc 5 -6和剂量补偿复合物，因其普遍存在而影响几乎所有的DNA稳态过程。虽然他们的精确的分子机制仍然是谜，在这里，我们提供了一个概述的架构真核Smc复合物，特别关注的cohesin，这已经看到了最近的进展。鉴于Smc复合物之间的许多结构特征的明显保守性，预计在破译其精确的分子机制时，结构和拓扑结构将具有重要作用。SMC二聚体复合物联合收割机与Kleisin家族的亚基结合并形成包埋DNA的环状复合物。在真核生物中，凝聚素、凝聚素和SMC 5 -6作用于姐妹染色单体凝聚、染色体凝聚和DNA修复。由于两种相反的活性，粘着蛋白复合物是动态的：由Scc 2-Scc 4复合物介导的DNA加载活性和由Pds 5-Wap 1-Scc 3复合物引发的释放活性。这些蛋白质的晶体结构提供了对其功能的深入了解。Pds 5和Scc 3在S期后的内聚维持中具有明显的正向作用。出现的概念是，这些复合物的不同排列存在于细胞周期的不同阶段。SMC以开放的V形和封闭的杆状形式存在，这可能代表复合物的功能状态。它们的形成依赖于与DNA和ATP水解的相互作用。
Cohesin facilitates sister chromatid cohesion through the formation of a large ring structure that encircles DNA. Its function relies on two structural maintenance of chromosomes (Smc) proteins, which are found in almost all organisms tested, from bacteria to humans. In accordance with their ubiquity, Smc complexes, such as cohesin, condensin, Smc5-6, and the dosage compensation complex, affect almost all processes of DNA homeostasis. Although their precise molecular mechanism remains enigmatic, here we provide an overview of the architecture of eukaryotic Smc complexes with a particular focus on cohesin, which has seen the most progress recently. Given the evident conservation of many structural features between Smc complexes, it is expected that architecture and topology will have a significant role when deciphering their precise molecular mechanisms. SMC dimeric complexes combine with a subunit of the kleisin family and form ring complexes entrapping DNA. In eukaryotes, cohesins, condensins, and SMC5-6 act on sister chromatid cohesion, chromosome condensation, and DNA repair. Cohesin complexes are dynamic as a result of two opposing activities: a DNA-loading activity mediated by the Scc2-Scc4 complex and a releasing activity elicited by the Pds5-Wapl-Scc3 complex. Crystal structures of these proteins are providing insight into their function. Pds5 and Scc3 have distinct positive functions in cohesion maintenance after S phase. The concept emerging is that different arrangements of these complexes exist in different stages of the cell cycle. SMCs are found in both open V-shaped and closed rod-shaped forms, which likely represent functional states of the complexes. Their formation depends on interactions with DNA and ATP hydrolysis.