The spindle checkpoint: two transitions, two pathways

The spindle checkpoint is an evolutionarily conserved mitotic regulatory mechanism that ensures that anaphase is not attempted until chromosomes are properly aligned on the spindle. Two different cell-cycle transitions must be inhibited by the spindle checkpoint to arrest cells at metaphase and prevent mitotic exit. The checkpoint proteins interact in ways that are more complex than was originally envisioned. This review summarizes the evidence for two pathways of spindle-checkpoint regulation in budding yeast. We describe how the proteins are involved in these pathways and discuss the ways in which the spindle checkpoint inhibits the cell-cycle machinery.