The mitotic spindle is built from microtubules and its dynamics are driven by members of the kinesin motor superfamily. An imbalance in the tight regulation of mitosis, or malfunction of a spindle component, results in incorrect chromosome segregation. Although segregation defects can lead to a range of cell fates, errors in mitosis can drive chromosomal instability, aneuploidy and cancer. The goal of this project is to use cryo-electron microscopy and biochemistry to reveal the mechanism of the mitotic kinesin CENPE, its susceptibility to inhibition, and to dissect the consequences of its inhibition on chromosomal instability in diverse cancer cell lines.
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