Metaphase Kinetochore Movements are Regulated by Kinesin-8 Motors and Microtubule Dynamic Instability

During metaphase, sister chromatids are connected to microtubules (MTs) extending from the opposite spindle poles via kinetochores, protein complexes on the chromosome. Kinetochores congress to the equatorial plane of the spindle and oscillate around it, with kinesin-8 motors restricting these movements. Yet, the physical mechanism underlying kinetochore movements is unclear. We show that kinetochore movements in the fission yeast Schizosaccharomyces pombe are regulated by kinesin-8-promoted MT catastrophe, force-induced rescue and MT dynamic instability [1]. A candidate screen showed that among the selected motors only kinesin-8 motors Klp5/Klp6 are required for kinetochore centering. Our theoretical model, which uses force-balance equations to calculate movements of kinetochores [2] and Langevin description of MT dynamic instability shows that kinesin-8 motors are required for kinetochore centering, whereas sensitivity of rescue to force is necessary for the generation of oscillations. We found that irregular kinetochore movements occur for a broader range of parameters than regular oscillations. Thus, our work provides an explanation for how regulation of MT dynamic instability contributes to kinetochore congression and the accompanying movements around the spindle center