He X, Patterson T E, Sazer S
Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):7965-70. doi: 10.1073/pnas.94.15.7965.
The spindle checkpoint monitors mitotic spindle integrity and the attachment of kinetochores to the spindle. Upon sensing a defect the checkpoint blocks cell cycle progression and thereby prevents chromosome missegregation. Previous studies in budding yeast show that the activated spindle checkpoint inhibits the onset of anaphase by an unknown mechanism. One possible target of the spindle checkpoint is anaphase promoting complex (APC), which controls all postmetaphase events that are blocked by spindle checkpoint activation. We have isolated mad2, a spindle checkpoint component in fission yeast, and shown that mad2 overexpression 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 factor inactivation, we present genetic evidence consistent with the hypothesis that the spindle checkpoint imposes a cell cycle arrest by inhibiting APC-dependent proteolysis.
纺锤体检查点监测有丝分裂纺锤体的完整性以及动粒与纺锤体的附着。一旦感知到缺陷，该检查点就会阻止细胞周期进程，从而防止染色体错误分离。以往在芽殖酵母中的研究表明，激活的纺锤体检查点通过未知机制抑制后期的开始。纺锤体检查点的一个可能靶点是后期促进复合体（APC），它控制着所有被纺锤体检查点激活所阻断的中期后事件。我们分离出了粟酒裂殖酵母中的纺锤体检查点组分mad2，并表明mad2的过表达激活了该检查点，并导致细胞周期在中期到后期的转变处停滞。除了观察到通过有丝分裂促进因子失活可以部分缓解mad2诱导的停滞外，我们还提供了遗传证据，支持纺锤体检查点通过抑制APC依赖的蛋白水解作用使细胞周期停滞的假说。
