Once a cell has successfully replicated its DNA, it must correctly segregate its chromosomes, a process guarded by the spindle assembly checkpoint. Sudakin et al. (page 925) have isolated and characterized a protein complex that appears to transmit an important signal in this checkpoint, findings that necessitate revising an earlier model. Tang et al. (Developmental Cell, 1:227–237) also examined the regulation of this checkpoint; the two papers are compared and discussed in a Comment by Hoyt (page 909).
Previous work suggested that unattached kinetochores caused the conversion of the Mad2 checkpoint protein to an activated form, which then bound to the anaphase-promoting complex or cyclosome (APC). In this model, interaction with activated Mad2 blocked the ubiquitin ligase activity of the APC, which is required for cells to complete mitosis. In...