Cell Cycle Control in Early Drosophila Development

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DESCRIPTION (provided by applicant): During development multicellular organisms must coordinate differentiation with cell proliferation, and the cell cycle is modified to achieve particular developmental goals. The regulation of two variant cell cycles is being investigated using Drosophila as a model: meiosis, a modified cell cycle in which two rounds of chromosome segregation permit the production of haploid gametes, and a rapid cell cycle used during early embryogenesis. The meiotic cell cycle is subject to developmental control to coordinate progression through meiosis with oocyte differentiation and fertilization. Understanding the control circuitry for these cycles will provide insights into causes of human infertility, and the regulatory genes identified are likely to be important in preventing cancer. Drosophila is an ideal model organism for the discovery of gene function because of the ready link between mutant recovery and protein identification. Cell cycle control genes identified in Drosophila most often have orthologs that play essential roles in humans. A protein kinase complex, PAN GU, drives the embryonic cycles by controlling translation of Cyclin B, a key protein that when complexed with the CDK1 kinase subunit promotes mitosis and inhibits DNA replication. The mechanism by which PAN GU regulates Cyclin B translation will be defined, elucidating the role of translational control in triggering the onset of mitosis. In the previous funding period mutants defective in controlling the meiotic cell cycle were recovered. Two of the affected proteins appear to be necessary for ubiquitin-mediated protein degradation. Their mechanisms of action will be determined and protein targets identified. This will reveal the role of protein degradation in meiotic chromosome segregation and lead to the identification of proteins critical for meiosis. The protein products of other genes necessary for the completion of meiosis and the restart of the cell cycle at fertilization will be isolated.