Figure 6.
Model illustrating the role of MDC1 and BRIT1 in maintaining centrosome integrity and cytokinesis. MDC1 and BRIT1 are both required for maintaining numerical centrosome homeostasis, mitotic spindle assembly, and cytokinesis by negatively regulating Aurora A and Plk1. Deficiency of MDC1 led to centrosome amplification followed by multipolar mitosis and chromosome missegregation resulting in aneuploidy. BRIT1 depletion led to misaligned spindles followed by spindle checkpoint activation. Because BRIT1 depletion also led to increased Aurora A and Plk1, the spindle checkpoint was eventually overcome and, in turn, triggered defective cytokinesis, leading to the generation of one polyploid cell.