ACTIVATION OF THE BUDDING YEAST SPINDLE ASSEMBLY CHECKPOINT WITHOUT MITOTIC SPINDLE DISRUPTION

The spindle assembly checkpoint keeps cells with defective spindles fr om initiating chromosome segregation. The protein kinase Mps1 phosphor ylates the yeast protein Mad1p when this checkpoint is activated, and the overexpression of Mps1p induces modification of Mad1p and arrests wild-type yeast cells in mitosis with morphologically normal spindles. Spindle assembly checkpoint mutants overexpressing Mps1p pass through mitosis without delay and can produce viable progeny, which demonstra tes that the arrest of wild-type cells results from inappropriate acti vation of the checkpoint in cells whose spindle is fully functional. E ctopic activation of cell-cycle checkpoints might be used to exploit t he differences in checkpoint status between normal and tumor cells and thus improve the selectivity of chemotherapy.