Tytell Jessica D, Sorger Peter K
Department of Biology and 2Biological Engineering Division Massachusetts Institute of Technology Cambridge MA 02139, USA.
J Cell Biol. 2006 Mar 13;172(6):861-74. doi: 10.1083/jcb.200509101.
Accurate chromosome segregation during mitosis requires biorientation of sister chromatids on the microtubules (MT) of the mitotic spindle. Chromosome-MT binding is mediated by kinetochores, which are multiprotein structures that assemble on centromeric (CEN) DNA. The simple CENs of budding yeast are among the best understood, but the roles of kinesin motor proteins at yeast kinetochores have yet to be determined, despite evidence of their importance in higher eukaryotes. We show that all four nuclear kinesins in Saccharomyces cerevisiae localize to kinetochores and function in three distinct processes. Kip1p and Cin8p, which are kinesin-5/BimC family members, cluster kinetochores into their characteristic bilobed metaphase configuration. Kip3p, a kinesin-8,-13/KinI kinesin, synchronizes poleward kinetochore movement during anaphase A. The kinesin-14 motor Kar3p appears to function at the subset of kinetochores that become detached from spindle MTs. These data demonstrate roles for structurally diverse motors in the complex processes of chromosome segregation and reveal important similarities and intriguing differences between higher and lower eukaryotes.
有丝分裂期间准确的染色体分离需要姐妹染色单体在有丝分裂纺锤体的微管(MT)上双定向排列。染色体与微管的结合由动粒介导,动粒是在着丝粒(CEN)DNA上组装的多蛋白结构。芽殖酵母的简单着丝粒是研究得最清楚的之一,尽管有证据表明驱动蛋白运动蛋白在高等真核生物中很重要,但它们在酵母动粒中的作用尚未确定。我们发现酿酒酵母中的所有四种核驱动蛋白都定位于动粒,并在三个不同的过程中发挥作用。驱动蛋白-5/BimC家族成员Kip1p和Cin8p将动粒聚集成其特征性的双叶中期构型。驱动蛋白-8、-13/KinI驱动蛋白Kip3p在后期A同步动粒向极运动。驱动蛋白-14马达蛋白Kar3p似乎在从纺锤体微管脱离的动粒亚群中起作用。这些数据证明了结构多样的马达蛋白在染色体分离复杂过程中的作用,并揭示了高等和低等真核生物之间重要的相似性和有趣的差异。