The RSC chromatin-remodelling complex influences mitotic exit and adaptation to the spindle assembly checkpoint by controlling Cdc14 phosphatase

Upon prolonged activation of the spindle assembly checkpoint (SAC) cells escape from mitosis through a mechanism called adaptation or mitotic slippage, which is thought to underlie the resistance of cancer cells to anti-mitotic drugs. We show that this mechanism in budding yeast this mechanism depends on known essential and non-essential regulators of mitotic exit, such as the FEAR pathway for the release of the Cdc14 phosphatase from the nucleolus in early anaphase. Moreover, the RSC chromatin-remodelling complex bound to its accessory subunit Rsc2 is involved in this process as a novel component of the FEAR pathway. We show that Rsc2 interacts physically with the polo kinase Cdc5, a major regulator of Cdc14, and is required for timely phosphorylation of the Cdc14 inhibitor Net1, which is important to free Cdc14 in the active form. Altogether, our data suggest that fine tuning regulators of mitotic exit play an important rolehave important functions during in mitotic progression ofin cells treated with microtubule poisons, and might be promising targets for cancer treatment.