A spindle checkpoint functions during mitosis in the early Caenorhabditis elegans embryo
A spindle checkpoint functions during mitosis in the early Caenorhabditis elegans embryo
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DOI：
10.1091/mbc.e04-08-0712
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发表时间：
2005-03-01
影响因子：
3.3
通讯作者：
Bowerman, B
中科院分区：
文献类型：
--
作者：
Encalada, SE;Willis, J;Bowerman, B
在有丝分裂期间，染色体分离由纺锤体检查点机制调节。该检查点延迟后期，直到所有动粒被来自两个纺锤体极的微管捕获，染色体大会到中期板，并且动粒和它们附着的微管之间的张力被正确地感知。虽然纺锤体检查点可以在许多不同的细胞类型中被激活，但这种调节机制在快速分裂的胚胎动物细胞中的作用仍然存在争议。在这里，使用活胚胎细胞的延时成像，我们表明，化学或突变破坏的有丝分裂纺锤体在早期秀丽隐杆线虫胚胎延迟通过有丝分裂的进展。通过降低有丝分裂纺锤体缺陷突变胚胎中保守检查点基因的功能，我们发现这些延迟需要纺锤体检查点。在没有功能检查点的情况下，在具有异常有丝分裂纺锤体的突变体中观察到染色体分离的更严重缺陷。我们还表明，保守的驱动蛋白CeMCAK，CENP-F相关蛋白HCP-1和HCP-2，以及核心动粒蛋白CeCENP-C都需要这个检查点。我们的分析表明，纺锤体检查点机制在早期动物胚胎的快速分裂细胞中起作用，并且该检查点可以防止有丝分裂期间的染色体分离缺陷。
During mitosis, chromosome segregation is regulated by a spindle checkpoint mechanism. This checkpoint delays anaphase until all kinetochores are captured by microtubules from both spindle poles, chromosomes congress to the metaphase plate, and the tension between kinetochores and their attached microtubules is properly sensed. Although the spindle checkpoint can be activated in many different cell types, the role of this regulatory mechanism in rapidly dividing embryonic animal cells has remained controversial. Here, using time-lapse imaging of live embryonic cells, we show that chemical or mutational disruption of the mitotic spindle in early Caenorhabditis elegans embryos delays progression through mitosis. By reducing the function of conserved checkpoint genes in mutant embryos with defective mitotic spindles, we show that these delays require the spindle checkpoint. In the absence of a functional checkpoint, more severe defects in chromosome segregation are observed in mutants with abnormal mitotic spindles. We also show that the conserved kinesin CeMCAK, the CENP-F-related proteins HCP-1 and HCP-2, and the core kinetochore protein CeCENP-C all are required for this checkpoint. Our analysis indicates that spindle checkpoint mechanisms are functional in the rapidly dividing cells of an early animal embryo and that this checkpoint can prevent chromosome segregation defects during mitosis.