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Abstract:
Work in a number of organisms has indicated that members of the Aurora kinase family are required for the correct bipolar segregation of sister chromatids in anaphase. In particular, Aurora kinases halt the cell cycle if sister chromatids are erroneously connected to the same pole, and are also required for correcting this error. However, the cell cycle delay, which occurs if kinetochores remain unconnected to microtubules, is largely independent of Aurora in budding yeast and human somatic cells. Contrasting with these findings, the fission yeast Aurora kinase Ark1 has been found to play a role in delaying the cell cycle when kinetochores are unattached (Petersen and Hagan, 2003). We have re-examined the phenotype of Ark1 inhibition in fission yeast mitosis and meiosis, using a temperature-sensitive allele and a small-molecule inhibitor, as well as meiosis- specific shut-down by promoter exchange. We find a clear defect in bipolar chromosome segregation in mitosis, consistent with Aurora’s role in other organisms. In meiosis I, Ark1 promotes the segregation of homologous chromosomes to opposite poles. However, when recombination and side-by-side-arrangement of kinetochores are abolished, so that mitosis-like chromosomes exist in a meiosis I cell, Ark1 promotes the bi-polar segregation of sister chromatids, indicating that Ark1 is able to function independently of the underlying kinetochore morphology. Furthermore, in both mitosis and meiosis, Ark1 is required to delay the cell cycle if microtubule-kinetochore interactions occur, but not in the proper bi-polar fashion. Together, this data demonstrates that the function of Aurora kinases is highly conserved in evolution. To further reveal the mechanism of action, we have extended our analysis of Ark1 by searching for genetic interactors, which has revealed candidates of downstream effectors.
