The role of microtubule-generated tension in accurate mitotic chromosome segregationMohan ‘Moe’ Gupta, Ph.D.
Iowa State University
Hosts: Linda Wordeman and Alex Paredez
To ensure genome stability in mitosis, the spindle assembly checkpoint (SAC) delays anaphase if sister chromosomes are not bound to microtubules from opposite spindle poles. Only in this configuration can dynamic microtubules produce tension across sister kinetochores. The interdependency between kinetochore-microtubule attachment and tension has proved challenging to elucidating the role(s) of tension at kinetochores. Thus, whether the SAC responds simply to kinetochore attachment status, or also to tension status remains obscure. Unlike higher eukaryotes, budding yeast kinetochores bind only one microtubule, simplifying the relationship between attachment and tension. To address the role of microtubule-generated tension in checkpoint signaling, we developed a Taxol-sensitive yeast model that allows tension to be reduced by microtubule stabilization in fully assembled spindles with attached kinetochores. Our results reveal that reducing tension on attached kinetochores delays anaphase onset. The tension-specific delay is transient relative to that imposed by kinetochores that are both unattached and tensionless. Furthermore, the mechanism requires only a subset of the core SAC proteins. Our results demonstrate that reduced tension generates a signal to delay anaphase that is temporally and mechanistically distinct from that characterized for unattached kinetochores.