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Coordinating cellular events during spore development

$464,083R15FY2025GMNIH

University Of Massachusetts Boston, Dorchester MA

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Abstract

Project Summary: This project will examine the regulation of the meiotic cell cycle. In the budding yeast Saccharomyces cerevisiae, meiosis occurs during sporulation, when a diploid mother cell will remodel its interior through meiosis and spore morphogenesis to create four haploid spores. At the completion of meiosis II, the cell will undergo spindle disassembly and cytokinesis. In the budding yeast, meiotic cytokinesis takes place through the closure of the prospore membrane, a membrane that is synthesized during sporulation and grows to surround the newly formed 1N DNA products of meiosis. Meiosis II spindle disassembly and timely prospore membrane closure are regulated by two pathways the work in parallel. The meiotic exit pathway involves Cdc15 (a Hippo-like kinase) acting upstream of Sps1 (a STE20- family GCKIII kinase). Interestingly, although Cdc15 is also used in mitotic exit as part of the Mitotic Exit Network, the downstream kinases it activates are not used for exit from meiosis. The second pathway involves Ama1, a meiosis-specific activator of the APC/C. For spindle disassembly, Ama1 and Sps1 regulate different targets and affect distinct aspects of spindle disassembly. This project will focus on two aspects of meiotic exit. First, the Cdc15-Sps1 pathway will be examined, to better understand Cdc15-Sps1 activation and how it affects spindle disassembly and prospore membrane closure. Second, we will examine microtubule binding proteins found on the meiosis II spindle, to better understand how spindle disassembly is regulated. The knowledge gained from this project will contribute to the fundamental understanding of meiotic cell cycle regulation and spindle disassembly and may contribute to our understanding of how hippo-like kinases and STE20-GCKIII kinases function. These studies will also contribute to our knowledge of fungal biology, which is important because fungi are commensal organisms (as part of the fungal microbiome) and can also become pathogenic.

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