Shugoshin prevents dissociation of cohesin from centromeres during mitosis in vertebrate cells.
Shugoshin prevents dissociation of cohesin from centromeres during mitosis in vertebrate cells.
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DOI：
10.1371/journal.pbio.0030086
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发表时间：
2005-03
期刊：
影响因子：
9.8
通讯作者：
Nasmyth K
中科院分区：
文献类型：
--
作者：
McGuinness BE;Hirota T;Kudo NR;Peters JM;Nasmyth K
姐妹染色单体之间的凝聚力是它们在有丝分裂纺锤体上双向取向的必要条件。它是由一个多亚基复合物称为cohesin介导的。在酵母中，在分裂后期开始时，粘着蛋白的α Kleisin亚基的蛋白水解裂解将粘着蛋白从着丝粒和染色体臂上去除，从而触发姐妹染色单体分离。在动物细胞中，大多数粘附素在前期通过涉及其Scc 3-SA 1/2亚基磷酸化的分离酶非依赖性途径从染色体臂上去除。着丝粒上的粘着蛋白对这一过程不敏感，并持续到中期，此时它的α Kleisin亚基被分离酶切割，这被认为是触发后期。是什么保护了着丝粒粘附素不受前期通路的影响？潜在的候选者是被称为shugoshins的蛋白质，其与果蝇MEI-S332和酵母Sgo 1蛋白质同源，其防止在第一次减数分裂时从着丝粒去除减数分裂粘着蛋白复合物。一种脊椎动物shugoshin样蛋白在分裂前期与着丝粒结合，在分裂后期开始时消失。RNA干扰导致HeLa细胞有丝分裂停滞。大多数染色体在中期板上双取向，但染色体着丝粒粘附素的过早丢失伴随着所有姐妹染色单体粘附力的丧失，单个染色单体从中期板的离开，以及永久性的细胞周期停滞，可能是由于纺锤体检查点的激活。值得注意的是，Scc 3-SA 2的有丝分裂磷酸化位点已突变为丙氨酸的版本的表达使姐妹染色单体凝聚力的过早丧失和缺乏shugoshin的细胞的有丝分裂停滞变得更加明显。这些数据表明，shugoshin阻止有丝分裂期间着丝粒处的粘着蛋白Scc 3-SA 2亚基的磷酸化。这确保了粘着蛋白在着丝粒上持续存在，直到分离酶的激活导致其α Kleisin亚基的裂解。着丝粒凝聚是有丝分裂染色体的标志之一。我们的研究结果表明，它不是一个内在稳定的属性，因为它可以很容易地被有丝分裂激酶破坏，这是在检查由shugoshin。Shugoshin通过保护粘连蛋白不被磷酸化来帮助保持新复制的染色体在一起，直到染色体分离的时刻到来。
Cohesion between sister chromatids is essential for their bi-orientation on mitotic spindles. It is mediated by a multisubunit complex called cohesin. In yeast, proteolytic cleavage of cohesin's α kleisin subunit at the onset of anaphase removes cohesin from both centromeres and chromosome arms and thus triggers sister chromatid separation. In animal cells, most cohesin is removed from chromosome arms during prophase via a separase-independent pathway involving phosphorylation of its Scc3-SA1/2 subunits. Cohesin at centromeres is refractory to this process and persists until metaphase, whereupon its α kleisin subunit is cleaved by separase, which is thought to trigger anaphase. What protects centromeric cohesin from the prophase pathway? Potential candidates are proteins, known as shugoshins, that are homologous to Drosophila MEI-S332 and yeast Sgo1 proteins, which prevent removal of meiotic cohesin complexes from centromeres at the first meiotic division. A vertebrate shugoshin-like protein associates with centromeres during prophase and disappears at the onset of anaphase. Its depletion by RNA interference causes HeLa cells to arrest in mitosis. Most chromosomes bi-orient on a metaphase plate, but precocious loss of centromeric cohesin from chromosomes is accompanied by loss of all sister chromatid cohesion, the departure of individual chromatids from the metaphase plate, and a permanent cell cycle arrest, presumably due to activation of the spindle checkpoint. Remarkably, expression of a version of Scc3-SA2 whose mitotic phosphorylation sites have been mutated to alanine alleviates the precocious loss of sister chromatid cohesion and the mitotic arrest of cells lacking shugoshin. These data suggest that shugoshin prevents phosphorylation of cohesin's Scc3-SA2 subunit at centromeres during mitosis. This ensures that cohesin persists at centromeres until activation of separase causes cleavage of its α kleisin subunit. Centromeric cohesion is one of the hallmarks of mitotic chromosomes. Our results imply that it is not an intrinsically stable property, because it can easily be destroyed by mitotic kinases, which are kept in check by shugoshin. Shugoshin helps to keep newly replicated chromosomes together by protecting cohesins from phosphorylation, until the moment for the chromosomes to separate has arrived
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DOI：
10.1083/jcb.140.5.1003
发表时间：
1998-03-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Moore DP;Page AW;Tang TT;Kerrebrock AW;Orr-Weaver TL
通讯作者：
Orr-Weaver TL
影响因子：
10.5
作者：
CohenFix, O;Peters, JM;Koshland, D
通讯作者：
Koshland, D
影响因子：
9.8
作者：
Hauf S;Roitinger E;Koch B;Dittrich CM;Mechtler K;Peters JM
通讯作者：
Peters JM
影响因子：
16
作者：
Haering, CH;Löwe, J;Nasmyth, K
通讯作者：
Nasmyth, K
影响因子：
30.8
作者：
Noma, K;Sugiyama, T;Grewal, SIS
通讯作者：
Grewal, SIS