Microtubule Dynamics, Kinetochore Number, and Kinetochore Distribution in Cells Undergoing Mitosis with Unreplicated Genomes

In cells undergoing mitosis with unreplicated genomes (MUG), anaphase is successfully initiated despite the abundance of kinetochores that are attached to microtubules emanating from both spindle poles (merotely). In cultured cells, merotely is associated with lagging at the metaphase plate. Treatment with microtubule-perturbing drugs alters the frequency of lagging, but the effect of these drugs on MUG cells is unclear. In this study, low doses of a microtubule-stabilizing drug, taxol, or a microtubule-destabilizing drug, nocodazole, dramatically increased the frequency of lagging kinetochores in the midbody of MUG daughter cell pairs. Likewise, increasing the kinetochore number increased the frequency of lagging kinetochores. In this thesis, these data are used to propose a model of mitosis in which the bipolar attachments of MUG cells are reduced to monopolar attachments that are stabilized by their perpendicular orientation with respect to the kinetochore, allowing for spindle assembly checkpoint satisfaction without centromeric tension