The Requirement for the Dam1 Complex Is Dependent upon the Number of Kinetochore Proteins and Microtubules
The Requirement for the Dam1 Complex Is Dependent upon the Number of Kinetochore Proteins and Microtubules
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DOI：
10.1016/j.cub.2011.04.002
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发表时间：
2011-05-24
期刊：
影响因子：
9.2
通讯作者：
Berman, Judith
中科院分区：
文献类型：
--
作者：
Burrack, Laura S.;Applen, Shelly E.;Berman, Judith
Dam1复合物将动粒连接到纺锤体微管上，并且在体外是一种持续合成能力因子[1,2]。在酿酒酵母（Saccharomyces cerevisiae）中，其具有连接到单根微管的点状着丝粒，任何Dam1复合物成员的缺失都会导致染色体分离失败和细胞死亡[3 - 5]。在粟酒裂殖酵母（Schizosaccharomyces pombe）中，其具有表观遗传定义的区域着丝粒，每个着丝粒连接3 - 5根动粒微管，Dam1复合物的同源物并非必需[6]。为了确定为什么该复合物在某些生物中是必需的而在其他生物中不是，我们使用了白色念珠菌（Candida albicans），这是一种具有连接到单根微管的区域着丝粒的多形性酵母[7]。有趣的是，Dam1复合物在白色念珠菌中是必需的，这表明每个着丝粒的微管数量对其需求至关重要。重要的是，通过提高CENP - A的表达水平，更多的动粒蛋白和微管被募集到着丝粒上，并且着丝粒仍然完全具有功能。此外，在具有额外动粒蛋白和微管的细胞中，Dam1复合物成员对生长的重要性降低。因此，对Dam1复合物的需求并非由于点状着丝粒的DNA特异性。相反，当染色体在每个着丝粒具有多个动粒复合物和微管时，Dam1复合物的重要性降低，这意味着它在体内和体外都作为一种持续合成能力因子发挥作用。
The Dam1 complex attaches the kinetochore to spindle microtubules and is a processivity factor in vitro [1, 2]. In Saccharomyces cerevisiae, which has point centromeres that attach to a single microtubule, deletion of any Dam1 complex member results in chromosome segregation failures and cell death [3-5]. In Schizosaccharomyces pombe, which has epigenetically defined regional centromeres that each attach to 3-5 kinetochore microtubules, Dam1 complex homologs are not essential [6]. To determine why the complex is essential in some organisms and not in others, we used Candida albicans, a multimorphic yeast with regional centromeres that attach to a single microtubule [7]. Interestingly, the Dam1 complex was essential in C. albicans, suggesting that the number of microtubules per centromere is critical for its requirement. Importantly, by increasing CENP-A expression levels, more kinetochore proteins and microtubules were recruited to the centromeres, which remained fully functional. Furthermore, Dam1 complex members became less crucial for growth in cells with extra kinetochore proteins and microtubules. Thus, the requirement for the Dam1 complex is not due to the DNA-specific nature of point centromeres. Rather, the Dam1 complex is less critical when chromosomes have multiple kinetochore complexes and microtubules per centromere, implying that it functions as a processivity factor in vivo as well as in vitro.