Kip3-ing kinetochores clustered.

Metaphase is the brief and highly conspicuous period during cell division where chromosomes become positioned at the spindle equator through the process of " congression ". it is generally believed that congression promotes accurate chromosome segregation during anaphase, and this logic has driven research over several decades to identify the underlying mechanisms. Recent studies have demonstrated that Kinesin-8 microtubule motors are important for congression in organisms ranging from fission yeast to humans, 1-3 and that they probably act by modulating the dynamics of kinetochore-microtubule plus ends where they concentrate. 2,4-6 it has been unclear, however , if this role is conserved in the budding yeast Saccharomyces cerevisiae. Previous work by Tytell and Sorger showed that kinetochores lag during mitosis in yeast cells lacking the Kinesin-8 Kip3, and they proposed that Kip3 synchronizes poleward kinetochore movements during anaphase. 7 Gardner et al. have suggested that Kip3 is not involved in kineto-chore positioning during pre-anaphase mito-sis, and that the primary function of Kip3 is to govern spindle length by regulating the dynamics of interpolar microtubules. 8 in Cell Cycle, Wargacki and colleagues demonstrate that Kip3 is required for chromosome congression like other Kinesin-8 motors.9 in budding yeast, metaphase sister kinetochores appear bi-lobed, forming clusters on either side of the spindle equator. Using quantitative fluorescence microscopy and live cell imaging, the authors find that kinetochores attach spindle microtubules normally in kip3Δ cells but are declustered (Fig. 1), indicating that kinetochores are scattered along the spindle axis in the mutant. This notion is confirmed through an analysis of single centromere (CEN3) positioning. Wargacki et al. show that KiP3 deletion causes CEN3 mis-positioning and, consistent with previous work, 7 that centromeric chromatin between sister kineto-chores is hyperstretched, an effect probably caused by abnormally high microtubule-induced pulling forces on kinetochores. A final important observation in the Wargacki et al. study is that spindle length is normal in kip3Δ cells, suggesting that Kip3-dependent effects on kinetochore positioning are not indirect consequences of inter-polar microtubule length regulation by the motor. Discrepancies between previous reports 8,10 are probably due to technical differences in how spindle lengths were measured; Wargacki et al. used spindle pole body markers instead of fluorescent tubulin to identify spindle poles. The work by Wargacki et al. is important because it establishes that Kip3, like the other Kinesin-8 motors analyzed to-date, performs a critical function during chromosome congression. it also supports the idea that proper kinetochore …