AEKSP · In depth analysis of the role of essential kinases in regulation of meiotic chromosome segregation in Schizosaccharomyces pombe

Meiosis is a specialized cell cycle that enables diploid organisms to reproduce sexually by generating haploid gametes through two succesive divisions. To depict the detailed regulatory mechanism of meiotic chromosome segregation, the relevant proteins need to be identified and characterized. Protein kinases play important role and regulate multiple biological processes, including meiosis. Up to now, several kinases have been shown to be implicated in regulation of meiotic chromosome segregation. However, some kinases are essential for mitotic growth, a fact that precluded their detailed analysis in meiosis.Recently, we applied high-throughput knockout and chemical genetic strategies to construct the conditional analog-sensitive mutants of all known Schizosaccharomyces pombe essential kinases. Inhibition of particular kinases during meiosis and analysis of meiotic chromosome segragation in these mutants revealed that eight of these kinases play essential role for faithful chromosome segregation.The proposed project aims to analyze in more detail the molecular functions of selected essential kinases and define how these kinases regulate meiotic chromosome segregation. To elucidate the regulatory functions of these kinases, their role in meiotic recombination, in mono-orientation of sister kinetochores and in protection of centromeric cohesion will be analyzed. In addition, the proteomic approach will be applied to gain further insights into the kinases functions through identification of kinases targets and their postranslational modifications.In regard to the proposed project, the expected results could help us to better understand the molecular mechanism how chromosome segregation is regulated during meiosis and in the long-run also the principles of gametogenesis as well as the reason of genetic disorders resulting from chromosome missegregation.