The DASH complex and Klp5/Klp6 kinesin coordinate bipolar chromosome attachment in fission yeast

The DASH complex and Klp5/Klp6 kinesin coordinate bipolar chromosome attachment in fission yeast
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DOI:
10.1038/sj.emboj.7600761
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发表时间:
2005-08-17
期刊:
影响因子:
11.4
通讯作者:
Millar, JBA
Millar, JBA
中科院分区:
生物学1区
文献类型:
--
作者:
Sanchez-Perez, I;Renwick, SJ;Millar, JBA

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我们发现DAM1的一个截短等位基因是cdc13-117(细胞周期蛋白B)和Mal3-1(EB-1)细胞对甲苯咪唑(一种微管毒素)敏感性的多拷贝抑制基因。我们发现,当细胞进入有丝分裂时,Dam1与纺锤体微管和动点的正端结合,这依赖于分裂酵母DASH复合体的其他成分,包括Ask1、Duo1、Spc34和Dad1。相比之下,Dad1在整个细胞周期中仍然与动粒结合,其关联依赖于Mis6和Mal2,而不是Mis12、Nuf2或Cnp1动粒蛋白。在缺乏DAM1或DASH复合体的其他成分的细胞中,由于纺锤体组装检查点的激活,后期延迟,经常观察到落后的姐妹染色单体,有时姐妹染色单体对分离到同一纺锤体极。我们发现,有丝分裂着丝粒相关的Klp5/Klp6动蛋白复合体在缺乏DASH复合体成分的细胞中是必不可少的。缺乏Dam1和Klp5的细胞在有丝分裂中经历第一个细胞周期停滞,原因是未能建立双极染色体附着。
We identified a truncated allele of dam1 as a multicopy suppressor of the sensitivity of cdc13-117 ( cyclin B) and mal3-1 (EB-1) cells to thiabendazole, a microtubule poison. We find that Dam1 binds to the plus end of spindle microtubules and kinetochores as cells enter mitosis and this is dependent on other components of the fission yeast DASH complex, including Ask1, Duo1, Spc34 and Dad1. By contrast, Dad1 remains bound to kinetochores throughout the cell cycle and its association is dependent on the Mis6 and Mal2, but not Mis12, Nuf2 or Cnp1, kinetochore proteins. In cells lacking Dam1, or other components of the DASH complex, anaphase is delayed due to activation of the spindle assembly checkpoint and lagging sister chromatids are frequently observed and occasionally sister chromatid pairs segregate to the same spindle pole. We find that the mitotic centromere-associated Klp5/Klp6 kinesin complex is essential in cells lacking components of the DASH complex. Cells lacking both Dam1 and Klp5 undergo a first cell cycle arrest in mitosis due to a failure to establish bipolar chromosome attachment.