THE SCHIZOSACCHAROMYCES-POMBE SPINDLE CHECKPOINT PROTEIN MAD2P BLOCKSANAPHASE AND GENETICALLY INTERACTS WITH THE ANAPHASE-PROMOTING COMPLEX

The spindle checkpoint monitors mitotic spindle integrity and the atta chment of kinetochores to the spindle. Upon sensing a defect the check point blocks cell cycle progression and thereby prevents chromosome mi ssegregation, Previous studies in budding yeast show that the activate d spindle checkpoint inhibits the onset of anaphase by an unknown mech anism. One possible target of the spindle checkpoint is anaphase promo ting complex (APC), which controls all postmetaphase events that are b locked by spindle checkpoint activation. We have isolated mad2, a spin dle checkpoint component in fission yeast, and shown that mad2 overexp ression activates the checkpoint and causes a cell cycle arrest at the metaphase-to-anaphase transition. In addition to the observation that mad2-induced arrest can be partially relieved by mitosis-promoting fa ctor inactivation, we present genetic evidence consistent with the hyp othesis that the spindle checkpoint imposes a cell cycle arrest by inh ibiting APC-dependent proteolysis.