Gay et al. construct a mathematical model that accurately describes how fission yeast chromosomes segregate during mitosis.
Sister chromatids must attach to microtubules from opposite spindle poles so that they will segregate to different daughter cells during anaphase. Gay et al. analyzed the dynamics of mitotic chromosomes and spindle microtubules in live fission yeast and used their measurements to build a model of chromosome segregation in silico. The model was based on the assumption that, early in mitosis, spindle microtubules attach to and detach from kinetochores at random. But the simulated chromosomes segregated promptly and faithfully as long as two activities were in place to limit incorrect kinetochore–microtubule attachments.
The first of these simulated activities was a “kinetochore orientation effect,” which reduced the formation of incorrect attachments by boosting the propensity of individual kinetochores to bind multiple microtubules emanating from the same spindle pole. The second key activity served to destabilize incorrect kinetochore–microtubule attachments in the absence of tension between sister chromatids, a function performed in vivo by the kinase Aurora B.
When these in silico mechanisms were not optimized to ensure accurate segregation, Gay et al. found that some kinetochores had links to both spindle poles at anaphase onset. But these kinetochores showed more attachments to microtubules from the correct spindle pole and were therefore more frequently pulled into the appropriate daughter cell to avoid chromosome mis-segregation.
In addition to replicating normal mitosis, Gay et al.’s model could also reproduce the abnormal chromosome segregation observed in cells treated with an Aurora B inhibitor. The authors now want to use their model to explain the mitotic phenotypes of various fission yeast mutants.