Function and regulation of the spindle positioning checkpoint (SPOC) kinase Kin4 of budding yeast

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The ability of cells to undergo asymmetric cell divisions and to form daughter cells of distinct cell fates is a conserved mechanism that is involved in the generation of cell diversity in multiand unicellular organisms. In most cell types the position of the spindle plays a crucial role in determining whether a cell will divide asymmetrically or symmetrically. A couple of years ago, I and others have identified the spindle position checkpoint (SPOC) as an essential mechanism that senses the position of the spindle in respect to the division axis of a budding yeast cell. If the spindle is misaligned the SPOC delays both the transition out of mitosis and cytokinesis.So far, only five SPOC components have been identified: the kinases Cdc5 (polo-like kinase), Elm1 and Kin4, the Bfa1-Bub2 GAP complex, and the PP2A subunit Rts1. The Kin4 kinase is a key SPOC component that counteracts the inactivation of Bfa1-Bub2 GAP complex by Cdc5 polo kinase. Rts1 and Elm1 regulate the localisation and activity of Kin4 kinase, respectively. Interestingly, a similar checkpoint mechanism involving the homologue of Kin4 might exist in Drosophila stem cells. The im-portance of this checkpoint for cell cycle regulation in higher eukaryotes is just emerging.Kin4 kinase functions at the centre of the SPOC coordinating correct spindle alignment and exit from mitosis. However, relatively little is know about how the position of the spindle controls Kin4 kinase. This project therefore aims to unravel the molecular mechanisms that regulate localisation and activity of Kin4 kinase under normal cell cycle progression and upon SPOC activation.