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William J. Palframan,1Janet B. Meehl,2Sue L. Jaspersen,3Mark Winey,2Andrew W. Murray1*
The spindle checkpoint delays cell cycle progression until microtubulesattach each pair of sister chromosomes to opposite poles ofthe mitotic spindle. Following sister chromatid separation,however, the checkpoint ignores chromosomes whose kinetochoresare attached to only one spindle pole, a state that activatesthe checkpoint prior to metaphase. We demonstrate that, in buddingyeast, mutual inhibition between the anaphase-promoting complex(APC) and Mps1, an essential component of the checkpoint, leadsto sustained inactivation of the spindle checkpoint. Mps1 proteinabundance decreases in anaphase, and Mps1 is a target of theAPC. Furthermore, expression of Mps1 in anaphase, or repressionof the APC in anaphase, reactivates the spindle checkpoint.This APC-Mps1 feedback circuit allows cells to irreversiblyinactivate the checkpoint during anaphase.
1 Department of Molecular and Cellular Biology, Biological Laboratories, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA. 2 MCD Biology, UCB 347, University of Colorado, Boulder, CO 80309, USA. 3 Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
* To whom correspondence should be addressed. E-mail: amurray{at}mcb.harvard.edu
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