The complete removal of cohesin from chromosome arms depends on separase
The complete removal of cohesin from chromosome arms depends on separase
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DOI：
10.1242/jcs.011528
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发表时间：
2007-12-01
影响因子：
4
通讯作者：
Hirota, Toru
中科院分区：
文献类型：
--
作者：
Nakajima, Masato;Kumada, Kazuki;Hirota, Toru
在有丝分裂中，内聚蛋白需要从染色体上移除，以使姐妹染色单体分离。在脊椎动物中，有两条途径参与这一过程。前期途径需要内聚蛋白亚基SA2和一种称为Wapl的内聚蛋白结合蛋白的磷酸化，在早期有丝分裂中从染色体臂上去除大部分内聚蛋白，并允许染色体臂的分离。在后期开始时，蛋白酶分离酶通过蛋白水解裂解另一个内聚蛋白亚基Scc1 （Rad21, Mcd1）去除富含着丝粒的内聚蛋白，从而使姐妹染色单体分离。当后期开始被纺锤体组装检查点延迟时，从染色体臂上而不是从着丝粒上完全去除内聚蛋白产生典型的X或v形染色体。在这里，我们发现，如果蛋白酶体抑制剂MG132阻止有丝分裂，染色体臂之间的内聚得以保留。这种臂内聚依赖于受shugoshin蛋白Sgo1保护的内聚蛋白复合物，在早期有丝分裂中，它似乎分布在染色体臂和着丝粒上。在缺乏分离酶或表达不可切割Scc1的细胞中，在诺可达唑阻滞期间，臂内聚不能有效去除。我们的观察结果表明，Sgo1保护臂内聚蛋白的一部分，这阻止了前期途径中的内聚蛋白被移除，分离酶在诺可达唑捕获的细胞中部分被激活，并移除受Sgo1保护的臂内聚蛋白。
Cohesin needs to be removed from chromosomes to allow sister chromatid separation in mitosis. In vertebrates, two pathways contribute to this process. The prophase pathway, which requires phosphorylation of the cohesin subunit SA2 and a cohesin-binding protein, called Wapl, removes the bulk of cohesin from the chromosome arms in early mitosis and allows the resolution of the chromosome arms. At anaphase onset, the protease separase removes centromere-enriched cohesin by proteolytic cleavage of another cohesin subunit, Scc1 (Rad21, Mcd1), which allows the separation of sister chromatids. When anaphase onset is delayed by the spindle-assembly checkpoint, the complete removal of cohesin from chromosome arms but not from centromeres generates typical X- or V-shaped chromosomes. Here, we found that cohesion between chromosome arms is preserved if mitosis is arrested with the proteasome inhibitor MG132. This arm cohesion depends on cohesin complexes that are protected by the shugoshin protein Sgo1, which appears to be distributed on chromosome arms as well as on centromeres in early mitosis. In cells lacking separase or expressing noncleavable Scc1, arm cohesion was not efficiently removed during nocodazole arrest. Our observations suggest that a fraction of arm cohesin is protected by Sgo1, which prevents cohesin from being removed by the prophase pathway, and that separase is partly activated in nocodazole-arrested cells and removes the arm cohesin protected by Sgo1.