Aurora B kinase-dependent recruitment of hZW10 and hROD to tensionless kinetochores
Aurora B kinase-dependent recruitment of hZW10 and hROD to tensionless kinetochores
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DOI：
10.1016/j.cub.2007.11.037
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发表时间：
2007-12-18
期刊：
影响因子：
9.2
通讯作者：
Chan, Gordon K.
中科院分区：
文献类型：
--
作者：
Famulski, Jakub K.;Chan, Gordon K.
有丝分裂检查点通过监测有丝分裂期间的两个关键事件来确保正确的染色体分离。一个是着丝粒附着在有丝分裂纺锤体上，第二个是染色体在中期板上的排列，导致姐妹着丝粒之间的张力（在[1，2]中综述）。已知有丝分裂检查点蛋白在未对齐的染色体上积累，这些染色体未实现适当的着丝粒-微管附着或在姐妹着丝粒之间建立足够水平的张力[3]。在这里，我们报告了hZW 10和hROD，进化上保守的FIZZ复合物的两个组分[4，5]，在着丝粒处积累以响应张力的丧失。通过使用活细胞成像和FRAP，我们发现hZW 10在无张力动粒上的积累源于动粒周转率的4倍降低。我们还发现，缺乏hZW 10的细胞逃避张力丧失诱导的有丝分裂检查点逮捕更迅速地比那些逮捕缺乏激动微管附件。此外，我们表明，在张力的情况下，但不是在没有着丝粒微管附件的情况下，药理学抑制极光B激酶活性与ZM 447439，导致hZW 10，hROD，和hBub 1从着丝粒的损失。因此，我们得出结论，极光B激酶活性所需的张力敏感的有丝分裂检查点的组件，如hZW 10和hROD的积累，以维持有丝分裂检查点逮捕。
The mitotic checkpoint ensures proper chromosome segregation by monitoring two critical events during mitosis. One is kinetochore attachment to the mitotic spindle, and the second is the alignment of chromosomes at the metaphase plate, resulting in tension across sister kinetochores (reviewed in [1, 2]). Mitotic-checkpoint proteins are known to accumulate at unaligned chromosomes that have not achieved proper kinetochore-microtubule attachments or established an adequate level of tension across sister kinetochores [3]. Here, we report that hZW10 and hROD, two components of the evolutionarily conserved FIZZ complex [4, 5], accumulate at kinetochores in response to the loss of tension. By using live-cell imaging and FRAP, we showed that the accumulation of hZW10 at tensionless kinetochores stems from a 4-fold reduction of kinetochore turnover rate. We also found that cells lacking hZW10 escape loss-of-tension-induced mitotic-checkpoint arrest more rapidly than those arrested in response to the lack of kinetochore-microtubule attachments. Furthermore, we show that pharmacological inhibition of Aurora B kinase activity with ZM447439 in the absence of tension, but not in the absence of kinetochore-microtubule attachments, results in the loss of hZW10, hROD, and hBub1 from kinetochores. We therefore conclude that Aurora B kinase activity is required for the accumulation of tension-sensitive mitotic-checkpoint components, such as hZW10 and hROD, in order to maintain mitotic-checkpoint arrest.