Spatiotemporal dynamics of Spc105 regulates the assembly of the Drosophila kinetochore.

Spatiotemporal dynamics of Spc105 regulates the assembly of the Drosophila kinetochore.
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DOI:
10.1098/rsob.110032
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发表时间:
2012-02
期刊:
影响因子:
5.8
通讯作者:
Glover DM
Glover DM
中科院分区:
生物学2区
文献类型:
--
作者:
Venkei Z;Przewloka MR;Ladak Y;Albadri S;Sossick A;Juhasz G;Novák B;Glover DM

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在每次细胞分裂前不久形成动粒是染色体正确分离的先决条件。果蝇合胞体胚胎的同步有丝分裂提供了一个理想的体内系统,以遵循动粒组装动力学,从而解决如何调控动粒形成的问题。我们发现,核排斥的Spc 105/KNL 1蛋白在间期防止早熟装配的Mis 12复合物。Spc 105在早期前期的核输入及其与着丝粒上的Mis 12复合体的直接关联因此是动粒组装的第一步。Spc 105和Mis 12复合物的累积动粒水平然后确定Ndc 80复合物募集仅在核膜破裂后开始的速率。Spc 105的羧基末端部分指导其核输入,并且当异位定位于中心体时,足以用于所有核心动粒组分和CENP-C的组装。超分辨率显微镜显示,Spc 105的羧基末端位于Mis 12和Ndc 80复合物的拉伸动粒的交界处。因此,我们的研究表明,动粒组件的物理访问起着至关重要的作用,在调节果蝇动粒组装,并导致我们的一个模型中,Spc 105是其发病的许可因素。
The formation of kinetochores shortly before each cell division is a prerequisite for proper chromosome segregation. The synchronous mitoses of Drosophila syncytial embryos have provided an ideal in vivo system to follow kinetochore assembly kinetics and so address the question of how kinetochore formation is regulated. We found that the nuclear exclusion of the Spc105/KNL1 protein during interphase prevents precocious assembly of the Mis12 complex. The nuclear import of Spc105 in early prophase and its immediate association with the Mis12 complex on centromeres are thus the first steps in kinetochore assembly. The cumulative kinetochore levels of Spc105 and Mis12 complex then determine the rate of Ndc80 complex recruitment commencing only after nuclear envelope breakdown. The carboxy-terminal part of Spc105 directs its nuclear import and is sufficient for the assembly of all core kinetochore components and CENP-C, when localized ectopically to centrosomes. Super-resolution microscopy shows that carboxy-terminus of Spc105 lies at the junction of the Mis12 and Ndc80 complexes on stretched kinetochores. Our study thus indicates that physical accessibility of kinetochore components plays a crucial role in the regulation of Drosophila kinetochore assembly and leads us to a model in which Spc105 is a licensing factor for its onset.
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