lncreased risk of slippage upon disengagement of the mitotic checkpoint.

lncreased risk of slippage upon disengagement of the mitotic checkpoint.

Blog Article

Drugs that impair microtubule dynamics alter microtubule-kinetochore attachment and invoke the mitotic checkpoint which arrests cells in mitosis.The arrest can last for hours, but it is leaky: cells adapt (i.e.

, slip out of it) and exit from mitosis.Here, we investigate the mechanism that allows Beta Glucan cells to escape, and whether it is possible to prevent it.Based on a model of the mitotic checkpoint which includes the presence of a positive feedback loop, the escape from the arrest is described as a stochastic transition driven by fluctuations of molecular components from a checkpoint ON to a checkpoint OFF state.

According to the model, drug removal further facilitates adaptation, cheese slicer a prediction we confirmed in budding yeast.The model suggests two ways to avoid adaptation: inhibition of APC/C and strengthening the mitotic checkpoint.We confirmed experimentally that both alterations decrease the chance of cells slipping out of mitosis, during a prolonged arrest and after washing out the drug.

Our results may be relevant for increasing the efficiency of microtubule depolymerizing drugs.