Regulation of mitotic chromosome cohesion by Haspin and Aurora B
Regulation of mitotic chromosome cohesion by Haspin and Aurora B
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DOI：
10.1016/j.devcel.2006.09.018
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发表时间：
2006-11-01
影响因子：
11.8
通讯作者：
Higgins, Jonathan M. G.
中科院分区：
文献类型：
--
作者：
Dai, Jun;Sullivan, Beth A.;Higgins, Jonathan M. G.
在脊椎动物的有丝分裂中，姐妹染色单体之间的结合分两个阶段丧失。在分裂前期和前中期，在Polo样激酶1和Aurora B的控制下，从染色体臂释放粘着蛋白，而Shugoshin被认为可以防止着丝粒粘着蛋白的去除，直到分裂后期。然而，维持着丝粒凝聚力的调节酶的描述并不完整。Haspin/Gsg 2是正常有丝分裂所需的组蛋白H3苏氨酸-3激酶。我们在这里报告，这两个H3苏氨酸-3磷酸化和粘着蛋白位于内部着丝粒。Haspin缺失破坏有丝分裂中的粘着蛋白结合和姐妹染色单体缔合，阻止正常的染色体排列并激活纺锤体组装检查点，导致在前中期样状态下停滞。Haspin的过表达阻碍了粘连蛋白的释放并稳定了臂的粘连。我们的结论是，Haspin是需要在有丝分裂过程中保持着丝粒凝聚力。我们还建议，极光B调节cohesin去除通过其对本地化的Shugoshin的影响。
In vertebrate mitosis, cohesion between sister chromatids is lost in two stages. In prophase and prometaphase, cohesin release from chromosome arms occurs under the control of Polo-like kinase 1 and Aurora B, while Shugoshin is thought to prevent removal of centromeric cohesin until anaphase. The regulatory enzymes that act to sustain centromeric cohesion are incompletely described, however. Haspin/Gsg2 is a histone H3 threonine-3 kinase required for normal mitosis. We report here that both H3 threonine-3 phosphorylation and cohesin are located at inner centromeres. Haspin depletion disrupts cohesin binding and sister chromatid association in mitosis, preventing normal chromosome alignment and activating the spindle assembly checkpoint, leading to arrest in a prometaphase-like state. Overexpression of Haspin hinders cohesin release and stabilizes arm cohesion. We conclude that Haspin is required to maintain centromeric cohesion during mitosis. We also suggest that Aurora B regulates cohesin removal through its effect on the localization of Shugoshin.