Abstract
The mitotic spindle is a force-generating molecular machine, and is built from microtubules which work together with members of the kinesin motor superfamily. An imbalance in the tight regulation of mitosis or force generation within the spindle, 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 force generation mechanism of the mitotic kinesin CENP-E, and to dissect the consequences of perturbation of this force generation on chromosomal segregation.
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