Chromosome Dynamics Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
EMBO J. 2013 Nov 13;32(22):2938-49. doi: 10.1038/emboj.2013.230. Epub 2013 Oct 18.
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.
黏合蛋白介导姐妹染色单体黏合,并通过 DNA 环化作用有助于有丝分裂间期染色质的组织。在脊椎动物体细胞中,黏合蛋白由 Smc1、Smc3、Rad21 和 SA1 或 SA2 组成。另外三个附加因子 Pds5、Wapl 和 Sororin 结合到黏合蛋白上,并调节其与染色质的动态关联。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 蛋白对于黏合蛋白乙酰转移酶 (CoATs) Esco1/2 允许 Smc3 乙酰化和 Sororin 结合,对于黏合的建立是必不可少的。虽然这两种蛋白都有助于端粒和臂的黏合,但 Pds5B 对于着丝粒的黏合是特异性所必需的。此外,在缺乏 Pds5B 的细胞中,Aurora B 在着丝粒区域的积累减少,损害了其错误修正功能,导致染色体错误分离和非整倍体。我们的工作支持了这样一个模型,即不同染色体区域的黏合蛋白复合物的组成和功能不同。