Requirement for PLK1 kinase activity in the maintenance of a robust spindle assembly checkpoint.

摘要: During mitotic arrest induced by microtubule targeting drugs, the weakening of spindle assembly checkpoint (SAC) allows cells to progress through cell cycle without chromosome segregation occurring. PLK1 kinase plays a major role in mitosis and emerging evidence indicates that is also involved establishing maintaining SAC signalling. However, mechanistically, not fully understood, with several recent reports indicating it can cooperate either one kinases, Aurora B or MPS1. In this study, we assess maintenance. We find nocodazole-arrested U2OS cells, activity continuously required for protein localisation at kinetochores. Consistent published data upon inhibition, phosphoThr3-H3, marker Haspin activity, reduced. Intriguingly, inhibition causes relocalise from kinetochores into fewer much larger foci, possibly due incomplete recruitment outer kinetochore proteins. Importantly, together partial B, efficient override occur. This phenotype more pronounced than observed combining same inhibitors MPS1 inhibition. does obviously promote override. These results indicate directly signalling, cooperating positive feedback loop partially redundant mechanisms exist which reinforce SAC.