Regulation of sister chromatid cohesion between chromosome arms
Regulation of sister chromatid cohesion between chromosome arms
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DOI：
10.1016/j.cub.2004.06.052
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发表时间：
2004-07-13
期刊：
影响因子：
9.2
通讯作者：
Peters, JM
中科院分区：
文献类型：
--
作者：
Giménez-Abián, JF;Sumara, I;Peters, JM
分裂后期姐妹染色单体的分离依赖于从染色体上去除粘连蛋白复合物[1]。在脊椎动物中，在前期和前中期，大部分的粘着蛋白已经从染色体臂上去除[2，3]，而粘着蛋白保留在着丝粒上，直到中期，当粘着蛋白被蛋白酶分离酶切割时[3，4]。在未受干扰的有丝分裂中，臂的凝聚力在整个中期仍然存在，并且基本上足以维持姐妹染色单体的凝聚力[5]。臂的凝聚力如何维持到分裂中期尚不清楚。在这里，我们表明，少量的凝聚素可以检测到的中期染色体臂的染色单体间区域。如果用微管毒物处理细胞延长前中期，这些粘着蛋白复合物就会从染色体臂上解离，臂的粘着性也会溶解。如果Plk 1的耗竭或Aurora B的抑制阻止了前中期阻滞细胞中的粘连蛋白解离，则臂的粘连得以维持。这些观察结果意味着，在未受干扰的有丝分裂，少量的凝聚保持手臂的凝聚力，直到中期。当缺乏Plk 1和Aurora B活性的细胞进入分裂后期时，染色单体失去粘着蛋白。蛋白酶体抑制剂可以防止这种损失，这意味着它依赖于分离酶的激活。因此，分离酶可能能够切割着丝粒和染色体臂上的粘着蛋白。
Sister chromatid separation in anaphase depends on the removal of cohesin complexes from chromosomes [1]. In vertebrates, the bulk of cohesin is already removed from chromosome arms during prophase and prometaphase [2,3], whereas cohesin remains at centromeres until metaphase, when cohesin is cleaved by the protease separase [3, 4]. In unperturbed mitoses, arm cohesion nevertheless persists throughout metaphase and is principally sufficient to maintain sister chromatid cohesion [5]. How arm cohesion is maintained until metaphase is unknown. Here we show that small amounts of cohesin can be detected in the interchromatid region of metaphase chromosome arms. If prometaphase is prolonged by treatment of cells with microtubule poisons, these cohesin complexes dissociate from chromosome arms, and arm cohesion is dissolved. If cohesin dissociation in prometaphase-arrested cells is prevented by depletion of Plk1 or inhibition of Aurora B, arm cohesion is maintained. These observations imply that, in unperturbed mitoses, small amounts of cohesin maintain arm cohesion until metaphase. When cells lacking Plk1 and Aurora B activity enter anaphase, chromatids lose cohesin. This loss is prevented by proteasome inhibitors, implying that it depends on separase activation. Separase may therefore be able to cleave cohesin at centromeres and on chromosome arms.