Regulation of microtubule growth rates and their impact on chromosomal instability

Microtubules are polymers of α/β tubulin dimers that build the mitotic spindle, which segregates duplicated chromosomes during cell division. Microtubule function is governed by dynamic instability, whereby cycles of growth and shrinkage contribute to the forces necessary for chromosome movement. Regulation of microtubule growth velocity requires cell cycle-dependent changes in expression, localization and activity of microtubule-associated proteins (MAPs) as well as tubulin post-translational modifications that modulate microtubule dynamics. It has become clear that optimal microtubule growth velocities are required for proper chromosome segregation and ploidy maintenance. Suboptimal microtubule growth rates can result from altered activity of MAPs and could lead to aneuploidy, possibly by disrupting the establishment of microtubule bundles at kinetochores and altering the mechanical forces required for sister chromatid segregation. Future work using high-resolution, low-phototoxicity microscopy and novel fluorescent markers will be invaluable in obtaining deeper mechanistic insights into how microtubule processes contribute to chromosome segregation.