Dewar Hilary, Tanaka Kozo, Nasmyth Kim, Tanaka Tomoyuki U
School of Life Sciences, University of Dundee, Wellcome Trust Biocentre, Dundee DD1 5EH, UK.
Nature. 2004 Mar 4;428(6978):93-7. doi: 10.1038/nature02328. Epub 2004 Feb 11.
The movement of sister chromatids to opposite spindle poles during anaphase depends on the prior capture of sister kinetochores by microtubules with opposing orientations (amphitelic attachment or bi-orientation). In addition to proteins necessary for the kinetochore-microtubule attachment, bi-orientation requires the Ipl1 (Aurora B in animal cells) protein kinase and tethering of sister chromatids by cohesin. Syntelic attachments, in which sister kinetochores attach to microtubules with the same orientation, must be either 'avoided' or 'corrected'. Avoidance might be facilitated by the juxtaposition of sister kinetochores such that they face in opposite directions; kinetochore geometry is therefore deemed important. Error correction, by contrast, is thought to stem from the stabilization of kinetochore-spindle pole connections by tension in microtubules, kinetochores, or the surrounding chromatin arising from amphitelic but not syntelic attachment. The tension model predicts that any type of connection between two kinetochores suffices for efficient bi-orientation. Here we show that the two kinetochores of engineered, unreplicated dicentric chromosomes in Saccharomyces cerevisiae bi-orient efficiently, implying that sister kinetochore geometry is dispensable for bi-orientation. We also show that Ipl1 facilitates bi-orientation by promoting the turnover of kinetochore-spindle pole connections in a tension-dependent manner.
在后期，姐妹染色单体向纺锤体两极的移动取决于先前微管以相反方向捕获姐妹动粒（双着丝粒附着或双定向）。除了动粒 - 微管附着所需的蛋白质外，双定向还需要Ipl1（动物细胞中的极光激酶B）蛋白激酶以及通过黏连蛋白连接姐妹染色单体。同着丝粒附着是指姐妹动粒以相同方向附着于微管，这种情况必须被“避免”或“纠正”。姐妹动粒并列排列使其朝向相反方向可能有助于避免同着丝粒附着；因此动粒的几何形状被认为很重要。相比之下，纠错被认为源于双着丝粒而非同着丝粒附着产生的微管、动粒或周围染色质中的张力对动粒 - 纺锤体极连接的稳定作用。张力模型预测，两个动粒之间的任何类型连接都足以实现有效的双定向。在此我们表明，酿酒酵母中经改造的未复制双着丝粒染色体的两个动粒能有效地双定向，这意味着姐妹动粒的几何形状对于双定向是可有可无的。我们还表明，Ipl1通过以张力依赖的方式促进动粒 - 纺锤体极连接的周转来促进双定向。
