Department of Genetics, Development and Cell Biology - Iowa State University
Host: Kristen Johansen
"The Role of Microtubule-generated Tension in the Spindle Assembly Checkpoint and Accurate Chromosome Segregation"
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 of kinetochore-microtubule attachment and tension has proved challenging to understanding SAC mechanisms. 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 tension in the SAC, 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 bipolar attached kinetochores delays anaphase onset. The tension-specific delay is transient relative to that imposed by the presence of both unattached and tensionless kinetochores. Furthermore, the mechanism requires the core SAC proteins Bub1 and Bub3, but not Mad1, Mad2 and Mad3 (yeast BubR1). These results demonstrate that reduced tension generates a ‘wait-anaphase’ signal that is temporally and mechanistically distinct from that characterized for unattached kinetochores.