| Popis: |
CDK1-cyclin B1 kinase is the main driver of mitosis and initiates the morphological changes that characterise mitosis, including mitotic spindle assembly and formation of the outer kinetochore. CDK1-cyclin B1 activity is also critically required for spindle assembly checkpoint (SAC) signalling during mitosis. In particular, CDK1-cyclin B1 promotes the targeting of the principal spindle checkpoint kinase MPS1 to kinetochores, leading to the recruitment of SAC proteins to the outer kinetochore scaffold protein KNL1 and initiation of checkpoint signalling. However, cells expressing kinetochore-tethered MPS1 still require CDK1 activity for SAC signalling, suggesting that CDK1 plays both MPS1-dependent and -independent roles in regulating the SAC. Here we show that the latter is due to CDK1-mediated kinetochore recruitment of KNL1, which is reversed by the PP1 phosphatase at the metaphase-to-anaphase transition. Our findings explain the abrupt and irreversible termination of spindle checkpoint signalling in anaphase, since the drop of CDK1 activity means both MPS1 and the spindle checkpoint scaffold KNL1 are lost from kinetochores.SummaryLim-Manley and Gruneberg investigate MPS1-independent roles of CDK1 in spindle checkpoint signalling. They reveal how PP1 activity following CDK1 inactivation results in the rapid removal of KNL1 from kinetochores at anaphase onset, contributing to prompt spindle checkpoint silencing. |
