Spindle checkpoint signaling requires the Mis6 kinetochore subcomplex, which interacts with Mad2 and mitotic spindles
Spindle checkpoint signaling requires the Mis6 kinetochore subcomplex, which interacts with Mad2 and mitotic spindles
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DOI：
10.1091/mbc.e05-01-0014
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发表时间：
2005-08-01
影响因子：
3.3
通讯作者：
Takahashi, K
中科院分区：
文献类型：
--
作者：
Saitoh, S;Ishii, K;Takahashi, K
纺锤体检查点通过抑制后期促进复合体/细胞周期体来协调细胞周期进程和染色体分离，直到所有动粒与纺锤体正确地相互作用。在有丝分裂早期，纺锤体检查点蛋白，如Mad 2和Bub 1，在不与纺锤体相关的动粒处积累。在这里，我们评估的要求，各种动粒组件的积累Mad 2和Bub 1上的动粒在裂变酵母，并表明Mis 6-复合物和Nuf 2-复合物的必要性是一个进化保守的功能在Mad 2上的动粒加载。此外，我们证明了Nuf 2是必需的维持Mis 6-复合物在有丝分裂的动粒。Mis 6复合物在Mad 2依赖性检查点被激活的条件下与Mad 2物理相互作用。异位表达的Mis 6的N-末端片段定位沿着有丝分裂纺锤体，突出Mis 6的潜在的结合能力，不仅对着丝粒染色质，而且对纺锤体微管。我们建议，Mis 6复杂，与Nuf 2复杂的合作，监测纺锤体-动粒附着状态，并作为一个平台，Mad 2积累在未附着的动粒。
The spindle checkpoint coordinates cell cycle progression and chromosome segregation by inhibiting anaphase promoting complex/cyclosome until all kinetochores interact with the spindle properly. During early mitosis, the spindle checkpoint proteins, such as Mad2 and Bub1, accumulate at kinetochores that do not associate with the spindle. Here, we assess the requirement of various kinetochore components for the accumulation of Mad2 and Bub1 on the kinetochore in fission yeast and show that the necessity of the Mis6-complex and the Nuf2-complex is an evolutionarily conserved feature in the loading of Mad2 onto the kinetochore. Furthermore, we demonstrated that Nuf2 is required for maintaining the Mis6-complex on the kinetochore during mitosis. The Mis6-complex physically interacts with Mad2 under the condition that the Mad2-dependent checkpoint is activated. Ectopically expressed N-terminal fragments of Mis6 localize along the mitotic spindle, highlighting the potential binding ability of Mis6 not only to the centromeric chromatin but also to the spindle microtubules. We propose that the Mis6-complex, in collaboration with the Nuf2-complex, monitors the spindle-kinetochore attachment state and acts as a platform for Mad2 to accumulate at unattached kinetochores.