Cohesin-dependent association of scc2/4 with the centromere initiates pericentromeric cohesion establishment.
Cohesin-dependent association of scc2/4 with the centromere initiates pericentromeric cohesion establishment.
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DOI：
10.1016/j.cub.2013.02.022
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发表时间：
2013-04-08
期刊：
影响因子：
9.2
通讯作者：
Marston, Adele L.
中科院分区：
文献类型：
--
作者：
Fernius, Josefin;Nerusheva, Olga O.;Galander, Stefan;Alves, Flavia de Lima;Rappsilber, Juri;Marston, Adele L.
黏连蛋白是一种保守的环状多蛋白复合物，参与染色体分离、DNA修复和转录调控。粘附素加载到染色体上普遍需要Scc 2/4“加载器”复合体（也称为NippedBL/Mau 2），该复合体的突变会导致人类发育障碍科尔内利亚·德兰格综合征。粘着蛋白主要集中在着丝粒周围，即围绕着丝粒的区域。富集的着丝粒周围粘附素需要芽殖酵母中的Ctf 19动粒亚复合物。在这里，我们发现的空间和时间的决定因素Scc 2/4着丝粒协会。我们证明了Ctf 19复合物的关键作用是使Scc 2/4与着丝粒结合，通过该结合，粘附素加载并扩散到相邻的着丝粒周围。我们发现，出乎意料的是，Scc 2与着丝粒的关联依赖于粘着蛋白本身。Scc 1/Mcd 1/Rad 21粘附素亚基的缺乏排除了Scc 2与着丝粒从后期到G1晚期的关联。SCC 1的表达对于粘附素与其装载剂的结合、Scc 2与着丝粒的结合以及粘附素装载是必要且充分的。我们建议，粘着蛋白触发其自身的负载，使Scc 2/4连接到染色体的地标，这在着丝粒指定的Ctf 19复合物。总的来说，我们的研究结果提供了一个范例的空间和时间控制的内聚素加载。Ctf 19动粒亚复合物将装载物靶向着丝粒Ctf 19动粒亚复合物将装载
Cohesin is a conserved ring-shaped multiprotein complex that participates in chromosome segregation, DNA repair, and transcriptional regulation. Cohesin loading onto chromosomes universally requires the Scc2/4 “loader” complex (also called NippedBL/Mau2), mutations in which cause the developmental disorder Cornelia de Lange syndrome in humans. Cohesin is most concentrated in the pericentromere, the region surrounding the centromere. Enriched pericentromeric cohesin requires the Ctf19 kinetochore subcomplex in budding yeast. Here, we uncover the spatial and temporal determinants for Scc2/4 centromere association. We demonstrate that the critical role of the Ctf19 complex is to enable Scc2/4 association with centromeres, through which cohesin loads and spreads onto the adjacent pericentromere. We show that, unexpectedly, Scc2 association with centromeres depends on cohesin itself. The absence of the Scc1/Mcd1/Rad21 cohesin subunit precludes Scc2 association with centromeres from anaphase until late G1. Expression of SCC1 is both necessary and sufficient for the binding of cohesin to its loader, the association of Scc2 with centromeres, and cohesin loading. We propose that cohesin triggers its own loading by enabling Scc2/4 to connect with chromosomal landmarks, which at centromeres are specified by the Ctf19 complex. Overall, our findings provide a paradigm for the spatial and temporal control of cohesin loading. ► Cohesin is required for the association of its loader, Scc2/4, with centromeres ► The Ctf19 kinetochore subcomplex targets the loader to centromeres ► Centromere-loaded cohesin ensures pericentromeric cohesion establishment ► Cohesin ring formation triggers cohesin loading via Scc2/4
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