Fission yeast kinesin-8 controls chromosome congression independently of oscillations.

Hadrien Mary,Jonathan Fouchard,Yannick Gachet,Guillaume Gay,Sylvie Tournier,Céline Reyes,Clémence Gruget,Tiphaine Gauthier,Jacques Pécréaux

doi:10.1242/jcs.160465

Abstract

ABSTRACTIn higher eukaryotes, efficient chromosome congression relies, among other players, on the activity of chromokinesins. Here, we provide a quantitative analysis of kinetochore oscillations and positioning in Schizosaccharomyces pombe, a model organism lacking chromokinesins. In wild-type cells, chromosomes align during prophase and, while oscillating, maintain this alignment throughout metaphase. Chromosome oscillations are dispensable both for kinetochore congression and stable kinetochore alignment during metaphase. In higher eukaryotes, kinesin-8 family members control chromosome congression by regulating their oscillations. By contrast, here, we demonstrate that fission yeast kinesin-8 controls chromosome congression by an alternative mechanism. We propose that kinesin-8 aligns chromosomes by controlling pulling forces in a length-dependent manner. A coarse-grained model of chromosome segregation implemented with a length-dependent process that controls the force at kinetochores is necessary and sufficient to mimic kinetochore alignment, and prevents the appearance of lagging chromosomes. Taken together, these data illustrate how the local action of a motor protein at kinetochores provides spatial cues within the spindle to align chromosomes and to prevent aneuploidy.

Highlights

Chromosome congression is an evolutionary conserved feature of mitosis thought to promote faithful segregation of sister chromatids into daughter cells (Kops et al, 2010)
Kinesin-8 actively controls and maintains kinetochore alignment during mitosis To explore the mechanisms controlling kinetochore alignment in S. pombe, we performed 3D live-cell imaging in wild-type and kinesin-8-deleted cells
With the heterodimeric association of Klp5 and Klp6, which is required for kinesin-8 function (Unsworth et al, 2008), both klp5Δ and klp5Δ klp6Δ double mutant showed the same deficiency in kinetochore centering (Fig. S1)

Summary

Introduction

Chromosome congression is an evolutionary conserved feature of mitosis thought to promote faithful segregation of sister chromatids into daughter cells (Kops et al, 2010). Efficient chromosome congression relies on multiple mechanisms and involves several microtubule (MT)-dependent motor proteins. A second mechanism of congression involves CENP-E at kinetochores mediating the sliding of chromosomes along spindle MTs (Cai et al, 2009; Kapoor et al, 2006). Received 24 July 2014; Accepted 3 September 2015 chromosome congression, bi-oriented sister kinetochores undergo oscillatory movements between the two spindle poles before chromosome segregation (Amaro et al, 2010; Pearson et al, 2001; Skibbens et al, 1993). Oscillations and congression of chromosomes are complex movements that require spatio-temporal control of tensional forces and attachment at the level of kinetochores that is far from being understood (Dumont and Mitchison, 2009). Chromosome oscillations are not absolutely required for the execution of mitosis given that several cell types seem to successfully segregate chromosomes in the absence of oscillations (Desai et al, 1998; LaFountain et al, 2001)

Methods

Results

Conclusion