Fig. 1

Different cell fate after prolonged mitosis and regulation of mitosis. a Graphic representation of the different cell fates after prolonged mitosis. Severe DNA damages or prolonged mitosis can induce direct apoptosis. Mitotically arrested cells can generate aneuploid cells due to premature cytokinesis or chromosome mis-segregation. Aneuploid cells may die during the next cell division or continue to proliferate as viable cells. Cells can overcome the arrest throughout the mitotic slippage generating tetraploid cells. These cells can arrest in interphase and eventually enter cellular senescence or die after slippage [10, 11]. b When the kinetochore is properly attached, CDC20 is released and activates APC/C that orchestrates cyclin B1 and securin degradation. Separase in turn degrades the cohesion complex at and near sister chromatid kinetochores promoting mitotic exit [6, 12]. c The SAC complex regulates mitosis. Restriction is achieved through inhibition of the activating APC/C-subunit CDC20. Loss of function of SAC proteins such as BUBR1, MAD2, or BUB1 (shown as red arrows) reduces the accuracy of SAC complex and, consequently, promotes genomic instability [13,14,15,16]. In parallel, the overexpression of mitotic kinases such as PLK1, Aurora A and B (shown in green arrows) enhances mitotic exit even in the presence of mitotic arrest [17,18,19,20,21,22]