Pds5B is required for cohesion establishment and Aurora B accumulation at centromeres
Pds5B is required for cohesion establishment and Aurora B accumulation at centromeres
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DOI：
10.1038/emboj.2013.230
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发表时间：
2013-11-13
期刊：
影响因子：
11.4
通讯作者：
Losada, Ana
中科院分区：
文献类型：
--
作者：
Carretero, Maria;Ruiz-Torres, Miguel;Losada, Ana
内聚蛋白介导姐妹染色单体内聚，并通过DNA环参与间期染色质的组织。在脊椎动物体细胞中，内聚蛋白由Smc1、Smc3、Rad21和SA1或SA2组成。另外三个因子Pds5， Wapl和Sororin结合到内聚蛋白并调节其与染色质的动态关联。在脊椎动物中有两种Pds5蛋白，Pds5A和Pds5B，但它们的功能特异性尚不清楚。在这里，我们证明Pds5蛋白通过允许Smc3被内聚蛋白乙酰转移酶（CoATs） Esco1/2乙酰化和Sororin结合，对内聚建立至关重要。虽然这两种蛋白质都有助于端粒和臂的内聚，但Pds5B是着丝粒内聚所特别需要的。此外，缺乏Pds5B的细胞内着丝粒区域Aurora B的积累减少，损害了其纠错功能，促进染色体错分离和非整倍体。我们的工作支持一个模型，其中的组成和功能的黏结蛋白复合物不同的染色体区域之间的差异。
Cohesin mediates sister chromatid cohesion and contributes to the organization of interphase chromatin through DNA looping. In vertebrate somatic cells, cohesin consists of Smc1, Smc3, Rad21, and either SA1 or SA2. Three additional factors Pds5, Wapl, and Sororin bind to cohesin and modulate its dynamic association with chromatin. There are two Pds5 proteins in vertebrates, Pds5A and Pds5B, but their functional specificity remains unclear. Here, we demonstrate that Pds5 proteins are essential for cohesion establishment by allowing Smc3 acetylation by the cohesin acetyl transferases (CoATs) Esco1/2 and binding of Sororin. While both proteins contribute to telomere and arm cohesion, Pds5B is specifically required for centromeric cohesion. Furthermore, reduced accumulation of Aurora B at the inner centromere region in cells lacking Pds5B impairs its error correction function, promoting chromosome mis-segregation and aneuploidy. Our work supports a model in which the composition and function of cohesin complexes differs between different chromosomal regions.