Figure 6. Proposed mechanism of how increased MT dynamics and SAC inhibition lead to synergistic toxicity by exacerbating the CIN phenotype.

(A) Cells with normal tubulin dynamics and a functional SAC have very low chromosome mis-segregation rates. (B) Cells with normal tubulin dynamics but with an alleviated SAC display intermediate chromosome mis-segregation. (C) Cells with high tubulin dynamics, but a functioning SAC correct unattached kinetochores before entering anaphase. (D) Cells with increased MT dynamics and an alleviated SAC suffer from increased numbers of unaligned chromosomes that are not signaled by the SAC leading to increased rates of chromosome mis-segregation.