The fission yeast DASH complex is essential for satisfying the spindle assembly checkpoint induced by defects in the inner-kinetochore proteins
The fission yeast DASH complex is essential for satisfying the spindle assembly checkpoint induced by defects in the inner-kinetochore proteins
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DOI：
10.1111/j.1365-2443.2007.01053.x
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发表时间：
2007-03-01
期刊：
影响因子：
2.1
通讯作者：
Takahashi, Kohta
中科院分区：
文献类型：
--
作者：
Kobayashi, Yasuyo;Saitoh, Shigeaki;Takahashi, Kohta
纺锤体装配检查点（SAC）是一种进化保守的染色体错分离监测系统。我们分离了裂变酵母Hos2， Dam1/DASH复合体的一个组成部分，作为nnf1-495突变体温度敏感（ts）生长的多拷贝抑制因子，该突变体表现出微染色体不稳定性（mis）表型，产生致命的非整倍体，没有明显的有丝分裂延迟。尽管存在错分离，但为什么SAC在错误突变体中仍然得到满足，这仍然是难以捉摸的。我们发现Hos2在前中期和中期都与内着丝点区域结合。Hos2对于Dis1的着丝点定位至关重要，Dis1是微管（MT）相关的Dis1/XMAP215/TOG家族蛋白，是MT动力学所必需的。缺乏DASH的细胞表现出冷敏感（cs）生长和姐妹染色单体分离（dis）表型的缺陷，其特征是超浓缩的姐妹染色单体对和细长的纺锤体mt。尽管DASH缺陷细胞在高温下存活，但DASH缺失将迄今为止测试的所有内着丝点错误突变体转化为SAC的组成活性状态，导致失表型。我们还发现，Hos2过表达通常抑制多种内着丝点突变体的生长迟缓。这些遗传相互作用突出了在有丝分裂过程中形成非整倍体时满足SAC的dash作用。
Spindle assembly checkpoint (SAC) is an evolutionarily conserved surveillance system for chromosome missegregation. We isolated fission yeast Hos2, a component of the Dam1/DASH complex, as a multicopy suppressor of temperature-sensitive (ts) growth of nnf1-495 mutant that exhibits the minichromosome instability (mis) phenotype, producing lethal aneuploids without prominent mitotic delay. It remains elusive why SAC is satisfied in mis mutants despite the occurrence of missegregation. We found that Hos2 binds to the inner-kinetochore regions in both prometaphase and metaphase. Hos2 is essential for kinetochore localization of Dis1, a microtubule (MT) associated Dis1/XMAP215/TOG family protein that is required for proper MT dynamics. Cells lacking DASH exhibit cold-sensitive (cs) growth with the defective in sister-chromatid disjoining (dis) phenotype, which is characterized by hyper-condensed sister-chromatid pairs and elongated spindle MTs. Although DASH-deficient cells are viable at high temperatures, DASH-deletion transforms all the inner-kinetochore mis mutants so far tested into a constitutively active state of SAC, leading to the dis phenotype. We also discovered that Hos2 over-expression commonly suppresses growth retardation in a variety of inner-kinetochore mutants. These genetic interactions highlight the DASH-action(s) in satisfying SAC when aneuploids are formed during mitosis in the inner-kinetochore-defective mis mutants.