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Proper chromosome segregation into two future daughter cells requires the mitotic spindle to elongate in anaphase. However, although some candidate proteins are implicated in this process, the molecular mechanism that drives spindle elongation in human cells is unknown. Using combined depletion and inactivation assays together with CRISPR technology to explore redundancy between multiple targets, we discovered that the force-generating mechanism of spindle elongation consists of EG5/kinesin-5 together with the PRC1-dependent motor KIF4A/kinesin-4, with contribution from kinesin-6 and kinesin-8. Disruption of EG5 and KIF4A leads to total failure of chromosome segregation due to blocked spindle elongation, despite poleward chromosome motion. Tubulin photoactivation, stimulated emission depletion (STED), and expansion microscopy show that perturbation of both proteins impairs midzone microtubule sliding without affecting microtubule stability. Thus, two mechanistically distinct sliding modules, one based on a self-sustained and the other on a crosslinker-assisted motor, power the mechanism that drives spindle elongation in human cells.

Original publication




Journal article


Dev Cell

Publication Date





1253 - 1267.e10


EG5/kinesin-5, KIF4A/kinesin-4, anaphase, anaphase B, functional redundancy, kinesins, microtubule sliding, mitosis, motor proteins, spindle elongation, Anaphase, Cell Cycle Proteins, Chromosome Segregation, Humans, Kinesins, Microtubule-Associated Proteins, Microtubules, Spindle Apparatus