Drosophila Mis12 Complex Acts as a Single Functional Unit Essential for Anaphase Chromosome Movement and a Robust Spindle Assembly Checkpoint
Drosophila Mis12 Complex Acts as a Single Functional Unit Essential for Anaphase Chromosome Movement and a Robust Spindle Assembly Checkpoint
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DOI：
10.1534/genetics.110.119628
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发表时间：
2011-01-01
期刊：
影响因子：
3.3
通讯作者：
Glover, David M.
中科院分区：
文献类型：
--
作者：
Venkei, Zsolt;Przewloka, Marcin R.;Glover, David M.
动粒是在有丝分裂中在着丝粒处组装的动态多蛋白复合物。在有丝分裂过程中，动粒的结构究竟如何变化，以及它的各个组成部分如何促进染色体分离，在很大程度上是未知的。在这里，我们集中在贡献的Mis12复杂的动粒组装和功能在果蝇有丝分裂。我们发现，尽管顺序着丝粒招聘的Mis12复杂的亚基Mis12和Nsl1，复杂的行为作为一个单一的功能单位。mis12和nsl 1突变体显示出惊人相似的发育和有丝分裂缺陷，其中染色体能够在中期大会，但它们的后期运动受到强烈影响。Ndc80的着丝粒结合完全依赖于Mis12和Nsl1，而BubR1定位仅显示部分依赖性。在残留的着丝粒BubR1的存在下，检查点仍然响应微管解聚，但显着较弱。这些观察结果表明，检查点反应的复杂性可能反映了与残留动粒成分、核心着丝粒或细胞中其他部位相关的BubR1亚群。重要的是，我们的研究结果表明，核心结构元件的动粒内板有更大的贡献，忠实的染色体分离在后期比在有丝分裂的早期阶段。
The kinetochore is a dynamic multiprotein complex assembled at the centromere in mitosis. Exactly how the structure of the kinetochore changes during mitosis and how its individual components contribute to chromosome segregation is largely unknown. Here we have focused on the contribution of the Mis12 complex to kinetochore assembly and function throughout mitosis in Drosophila. We show that despite the sequential kinetochore recruitment of Mis12 complex subunits Mis12 and Nsl1, the complex acts as a single functional unit. mis12 and nsl1 mutants show strikingly similar developmental and mitotic defects in which chromosomes are able to congress at metaphase, but their anaphase movement is strongly affected. While kinetochore association of Ndc80 absolutely depends on both Mis12 and Nsl1, BubR1 localization shows only partial dependency. In the presence of residual centromeric BubR1 the checkpoint still responds to microtubule depolymerization but is significantly weaker. These observations point to a complexity of the checkpoint response that may reflect subpopulations of BubR1 associated with residual kinetochore components, the core centromere, or elsewhere in the cell. Importantly our results indicate that core structural elements of the inner plate of the kinetochore have a greater contribution to faithful chromosome segregation in anaphase than in earlier stages of mitosis.