Zwint-1 is required for spindle assembly checkpoint function and kinetochore-microtubule attachment during oocyte meiosis.
Zwint-1 is required for spindle assembly checkpoint function and kinetochore-microtubule attachment during oocyte meiosis.
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DOI：
10.1038/srep15431
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发表时间：
2015-10-21
影响因子：
4.6
通讯作者：
Su Oh J
中科院分区：
文献类型：
--
作者：
Woo Seo D;Yeop You S;Chung WJ;Cho DH;Kim JS;Su Oh J
减数分裂中染色体可靠分离的关键步骤是动粒组装。这个过程中的缺陷导致非整倍体，导致流产，不孕和各种出生缺陷。然而，着丝粒在减数分裂过程中同源染色体分离中的作用尚不清楚。在这里，我们发现，Zwint-1是必需的同源染色体分离减数分裂过程中。Zwint-1的敲除通过废除Mad 2的动粒募集来加速第一次减数分裂，导致染色体错配和非整倍体的高发生率。虽然Zwint-1敲低不影响极光C激酶活性，但Zwint-1敲低后的减数分裂缺陷与用ZM 447439处理观察到的那些相似。重要的是，极光C激酶抑制后的染色体错位没有恢复Zwint-1敲低的卵母细胞中的抑制剂去除后，而在控制卵母细胞中的抑制剂洗脱后，挽救的缺陷。这些结果表明，极光C激酶介导的纠正错误的运动舞蹈微管附着主要是由Zwint-1调节。我们的研究结果提供了第一个证据，Zwint-1是需要纠正错误的着丝粒微管附件和调节纺锤体检查点功能在减数分裂。
The key step for faithful chromosome segregation during meiosis is kinetochore assembly. Defects in this process result in aneuploidy, leading to miscarriages, infertility and various birth defects. However, the roles of kinetochores in homologous chromosome segregation during meiosis are ill-defined. Here we found that Zwint-1 is required for homologous chromosome segregation during meiosis. Knockdown of Zwint-1 accelerated the first meiosis by abrogating the kinetochore recruitment of Mad2, leading to chromosome misalignment and a high incidence of aneuploidy. Although Zwint-1 knockdown did not affect Aurora C kinase activity, the meiotic defects following Zwint-1 knockdown were similar to those observed with ZM447439 treatment. Importantly, the chromosome misalignment following Aurora C kinase inhibition was not restored after removing the inhibitor in Zwint-1-knockdown oocytes, whereas the defect was rescued after the inhibitor washout in the control oocytes. These results suggest that Aurora C kinase-mediated correction of erroneous kinetochore-microtubule attachment is primarily regulated by Zwint-1. Our results provide the first evidence that Zwint-1 is required to correct erroneous kinetochore-microtubule attachment and regulate spindle checkpoint function during meiosis.