Functional characterization of the role of yeast aspin(s) in mitosis : doctorate in genetic and biomolecular sciences : phd thesis

Regulation of cell polarity and cell division axis is fundamental for stem cells and is frequently altered in malignant cells. These processes are tightly linked to control of spindle orientation. Haspin is an atypical protein kinase involved in mitosis; however, its precise role in the process is unknown. Here we demonstrate that Haspin regulates mitotic spindle orientation in yeast and human cells. Yeast Haspin mutants fail to elicit a functional spindle positioning checkpoint and divide the nucleus within a single cell body. We provide evidence indicating that Haspin positively regulates the Cdc42 GTPase, while it inhibits Cdc5 Pololike kinase. Depletion of Haspin interferes with the integrin-dependent mechanism that modulates spindle orientation in human epithelial cells, causing a spindle misorientation phenotype. This work establish the first role for yeast Haspin and an unexpected function for human Haspin, providing new insights in the pathway that, controlling spindle orientation, dictates the cell division axis in human cells.