Figure 1. Pathways to aneuploidization.

There are several pathways by which cells may gain or lose chromosomes during mitosis. A. Defects in mitotic checkpoint signaling. A weakened mitotic checkpoint may allow cells to enter anaphase in the presence of unattached or misaligned chromosomes. As a consequence, both copies of one chromosome may be deposited into a single daughter cell. B. Cohesion defects. If sister chromatid cohesion is lost prematurely or persists during anaphase then chromosomes may be missegregated. C. Merotelic attachment. One kinetochore may attach to microtubules from both poles of the spindle. If these attachments persist into anaphase then lagging chromatid pairs may be missegregated or excluded from both daughter cells during cytokinesis. D. Multipolar mitotic divisions. Cells possessing more than two centrosomes may form multiple spindle poles during mitosis. If this defect is not corrected, then a multipolar division will occur resulting in the production of highly aneuploid and often inviable daughter cells. Often, however, centrosomes in multipolar spindles cluster into two groups to allow cells to divide in a bipolar fashion. Centrosome clustering will increase the formation of incorrect kinetocore-microtubule attachments (such as merotelic attachments). Extra centrosomes are thus, capable of driving low rates of chromosome missegregation through a mechanism independent of multipolar divisions.