The human kinetochore proteins Nnf1R and Mcm21R are required for accurate chromosome segregation
The human kinetochore proteins Nnf1R and Mcm21R are required for accurate chromosome segregation
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DOI：
10.1038/sj.emboj.7601293
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发表时间：
2006-09-06
期刊：
影响因子：
11.4
通讯作者：
Sorger, Peter K.
中科院分区：
文献类型：
--
作者：
McAinsh, Andrew D.;Meraldi, Patrick;Sorger, Peter K.
着丝粒 (KT) 在着丝粒 DNA 上组装，双向配对姐妹染色单体在纺锤体微管 (MT) 上组装，并通过纺锤体组装检查点控制细胞周期进程。对芽殖酵母的遗传和生化研究已经证实，三种“连接子”复合物：MIND、COMA 和 NDC80，在 KT 组装和染色体分离中发挥重要但独特的作用。为了确定人类 KT 中是否存在类似的连接子活性，我们比较了 Nnf1R 和 Mcm21R（最近鉴定的 MIND 和 COMA 亚基）和 Nuf2R（一种充分表征的 NDC80 亚基）的功能。我们发现这三种蛋白质彼此独立地与 KT 结合，并且具有不同的细胞周期特征。 MT-KT 附着在 Nnf1R 和 Mcm21R 耗尽的细胞中是异常的，而在缺乏 Nuf2R 的情况下它会丢失。 Nnf1R 缺失的细胞中的缺陷附着会阻止染色体会聚，而 Mcm21R 缺失的细胞中的附着缺陷会干扰纺锤体组装。所有三种人类 KT 蛋白都是纺锤体检查点蛋白与 KT 正确结合所必需的。 Nnf1R、Mcm21R 和 Nuf2R 的不同功能和 KT 结合特性表明，与它们的酵母对应物一样，这些蛋白质在 KT 组装中彼此独立地发挥作用，但它们的组合活性是检查点信号传导所必需的。
Kinetochores (KTs) assemble on centromeric DNA, bi-orient paired sister chromatids on spindle microtubules (MTs) and control cell-cycle progression via the spindle assembly checkpoint. Genetic and biochemical studies in budding yeast have established that three 'linker' complexes, MIND, COMA and NDC80, play essential but distinct roles in KT assembly and chromosome segregation. To determine whether similar linker activities are present at human KTs, we have compared the functions of Nnf1R and Mcm21R, recently identified MIND and COMA subunits, and Nuf2R, a well-characterized NDC80 subunit. We find that the three proteins bind to KTs independent of each other and with distinct cell-cycle profiles. MT-KT attachment is aberrant in Nnf1R- and Mcm21R-depleted cells, whereas it is lost in the absence of Nuf2R. Defective attachments in Nnf1R- depleted cells prevent chromosome congression, whereas those in Mcm21R-depleted cells interfere with spindle assembly. All three human KT proteins are necessary for correct binding of spindle checkpoint proteins to KTs. The differing functions and KT-binding properties of Nnf1R, Mcm21R and Nuf2R suggest that, like their yeast counterparts, the proteins act independent of each other in KT assembly, but that their combined activities are required for checkpoint signaling.