Human Bub1 defines the persistent cohesion site along the mitotic chromosome by affecting shugoshin localization
Human Bub1 defines the persistent cohesion site along the mitotic chromosome by affecting shugoshin localization
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DOI：
10.1016/j.cub.2004.12.044
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发表时间：
2005-02-22
期刊：
影响因子：
9.2
通讯作者：
Watanabe, Y
中科院分区：
文献类型：
--
作者：
Kitajima, TS;Hauf, S;Watanabe, Y
Shugoshin（Sgo）蛋白构成了一个保守的蛋白质家族，被定义为减数分裂中含Rec 8粘附素复合物的着丝粒保护蛋白[1-4]。在脊椎动物有丝分裂中，含有Scc 1/Rad 21的粘着蛋白复合物在着丝粒处也受到保护，因为臂粘着蛋白而不是着丝粒粘着蛋白在前中期和前中期大部分解离[5，6]。解离过程依赖于polo样激酶（PIK 1）的活性，部分依赖于Aurora B [7-9]。最近，已经证明脊椎动物shugoshin是在有丝分裂期间保持着丝粒粘附所必需的[10];然而，没有解决人类shugoshin是否保护粘附素本身。在这里，我们表明，在有丝分裂的着丝粒人类Scc 1的持久性确实依赖于人类Sgo 1。在裂殖酵母中，Sgo定位依赖于Bub 1，一种保守的纺锤体检查点蛋白，它也是脊椎动物细胞前中期染色体聚集所需的。我们证明，人Sgo 1未能本地化在着丝粒在Bub 1抑制细胞，和着丝粒凝聚力显着松动。值得注意的是，在这些细胞中，Sgo 1重新定位到染色体的所有沿着其长度和激发异位保护从染色体臂上的Scc 1解离。这些结果揭示了迄今为止隐藏的作用，人类Bub 1在定义持久的凝聚力网站的有丝分裂染色体。
Shugoshin (Sgo) proteins constitute a conserved protein family defined as centromeric protectors of Rec8-containing cohesin complexes in meiosis [1-4]. In vertebrate mitosis, Scc1 /Rad21 -containing cohesin complexes are also protected at centromeres because arm cohesin, but not centromeric cohesin, is largely dissociated in pro- and prometaphase [5, 6]. The dissociation process is dependent on the activity of polo-like kinase (PIk1) and partly dependent on Aurora B [7-9]. Recently, it has been demonstrated that vertebrate shugoshin is required for preserving centromeric cohesion during mitosis [10]; however, it was not addressed whether human shugoshin protects cohesin itself. Here, we show that the persistence of human Scc1 at centromeres in mitosis is indeed dependent on human Sgo1. In fission yeast, Sgo localization depends on Bub1, a conserved spindle checkpoint protein, which is enigmatically also required for chromosome congression during prometaphase in vertebrate cells. We demonstrate that human Sgo1 fails to localize at centromeres in Bub1-repressed cells, and centromeric cohesion is significantly loosened. Remarkably, in these cells, Sgo1 relocates to chromosomes all along their length and provokes ectopic protection from dissociation of Scc1 on chromosome arms. These results reveal a hitherto concealed role for human Bub1 in defining the persistent cohesion site of mitotic chromosomes.