During mitosis, several morphologically distinct events must occur in the right order. For example, chromosome segregation must be complete before cytokinesis. Two papers on this mitotic coordination, one by Norden et al. and the other by Mendoza et al., stirred a memory of a discussion that I had with my graduate mentor, Professor Mitsuhiro Yanagida.

Yanagida-sensei suggested ... that cut1 may be a component of the checkpoint that delays cytokinesis in the presence of unsegregated chromosomes.

Studying fission yeast Cut1 (cell untimely torn 1; now known as separase or separin, the protease that cleaves sister chromatid linkages), I naively thought that, after anaphase is triggered, there is no feedback between chromosome segregation and cytokinesis. One evening in 1994, Yanagida-sensei suggested to me that Cut1 may be a component of the checkpoint that delays cytokinesis in the presence of unsegregated chromosomes. This would explain why cut1 mutants showed the cut phenotype, in which cytokinesis takes place over the unseparated chromosomes. I pushed aside this idea, however, as cut phenotypes were so prevalent in other fission yeast mutants, such as the DNA topoisomerase II mutant top2.

More than a decade later, I was stunned by the report from Norden et al., demonstrating the existence of just such a checkpoint, NoCut, in budding yeast. In the study by Mendoza et al., the same group further showed that the non-catalytic function of Esp1 (the budding yeast separase) is actually important for the NoCut checkpoint. Their results indicate that the separase–Cdc14 early anaphase release (FEAR) pathway promotes recruitment of the protein kinase increase-in-ploidy 1 (Ipl1; also known as Aurora B) to the spindle midzone, which activates this checkpoint in the presence of unsegregated chromosomes. Interestingly, unlike the case in fission yeast, NoCut inhibits completion of cytokinesis in the budding yeast top2 mutant. So, I had a good reason to miss this checkpoint in fission yeast, but my supervisor had the right perspective. A study by Steigemann et al. suggests that a similar checkpoint exists even in human cells, although in this case the direct involvement of separase in the NoCut checkpoint remains an open question.