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Science 16 August 1996:
Vol. 273. no. 5277, pp. 953 - 956
DOI: 10.1126/science.273.5277.953

Reports

Activation of the Budding Yeast Spindle Assembly Checkpoint Without Mitotic Spindle Disruption

Kevin G. Hardwick, * Eric Weiss, * Francis C. Luca, Mark Winey, Andrew W. Murray dagger

The spindle assembly checkpoint keeps cells with defective spindles from initiating chromosome segregation. The protein kinase Mps1 phosphorylates 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 demonstrates that the arrest of wild-type cells results from inappropriate activation of the checkpoint in cells whose spindle is fully functional. Ectopic activation of cell-cycle checkpoints might be used to exploit the differences in checkpoint status between normal and tumor cells and thus improve the selectivity of chemotherapy.

K. G. Hardwick and A. W. Murray, Department of Physiology, University of California, San Francisco, CA 94143-0444, USA.
E. Weiss, F. C. Luca, M. Winey, Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309-0347, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed.



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