Astrin is required for the maintenance of sister chromatid cohesion and centrosome integrity.
Astrin is required for the maintenance of sister chromatid cohesion and centrosome integrity.
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DOI：
10.1083/jcb.200701163
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发表时间：
2007-07-30
期刊：
影响因子：
--
通讯作者：
Gruneberg U
中科院分区：
文献类型：
--
作者：
Thein KH;Kleylein-Sohn J;Nigg EA;Gruneberg U
在有丝分裂中，染色体的可靠分离需要形成具有稳定附着的染色体的双极有丝分裂纺锤体。一旦所有染色体对齐，姐妹染色单体之间的连接就会被半胱氨酸蛋白酶分离酶切断。分离酶也促进中心粒在有丝分裂结束时脱离。有丝分裂的成功完成需要这两种活动与细胞周期的其余部分的时间协调。在这项研究中，我们报告说，耗尽的微管和动粒蛋白astrin的检查点逮捕的细胞与多极纺锤体和分离的姐妹染色单体，这是一致的不合时宜的分离酶激活。支持这一观点的是，缺乏收敛蛋白的细胞含有活性分离酶，而分离酶的缺乏抑制了这些细胞中姐妹染色单体的过早分离和中心粒的分离。我们认为，astrin有助于控制分离酶活性的调节网络。
Faithful chromosome segregation in mitosis requires the formation of a bipolar mitotic spindle with stably attached chromosomes. Once all of the chromosomes are aligned, the connection between the sister chromatids is severed by the cysteine protease separase. Separase also promotes centriole disengagement at the end of mitosis. Temporal coordination of these two activities with the rest of the cell cycle is required for the successful completion of mitosis. In this study, we report that depletion of the microtubule and kinetochore protein astrin results in checkpoint-arrested cells with multipolar spindles and separated sister chromatids, which is consistent with untimely separase activation. Supporting this idea, astrin-depleted cells contain active separase, and separase depletion suppresses the premature sister chromatid separation and centriole disengagement in these cells. We suggest that astrin contributes to the regulatory network that controls separase activity.