REGULATION OF THE MEIOTIC CELL CYCLE

Massachusetts Institute Of Technology, Cambridge MA

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Abstract

DESCRIPTION: During the mitotic cycle a single round of DNA replication is followed by a chromosome segregation phase, during which the duplicated genetic material is partitioned between the daughter cells. Meiosis is a specialized cell cycle in which a single DNA replication phase precedes two consecutive chromosome segregation phases. Meiosis-specific regulators of chromosome segregation are likely to act on the machinery common to mitotic and meiotic chromosome segregation to bring about the meiotic chromosome segregation program. A specialized ubiquitin-dependent proteolysis machinery, the APC (anaphase promoting complex), is a key regulator of chromosome segregation during mitosis. In Saccharomyces cerevisiae, the Pi has shown that the APC regulates meiotic recombination, which is critical for the first meiotic chromosome segregation phase. The protein Spo13 is a meiosis-specific regulator of chromosome segregation. The goals of this proposal are (1) to determine the role of the APC during meiotic recombination, (2) to determine how Spo13 controls meiotic chromosome segregation and (3) to identify new genes that regulate meiotic chromosome segregation. To characterize the role of the APC during meiotic recombination, genetic and molecular assays for recombination will be used to determine the step during recombination at which the APC is required. Biochemical and genetic approaches will then be used to identify APC target(s) whose destruction is required for the execution of meiotic recombination. Two approaches will be taken to identify meiosis-specific regulators of chromosome segregation. First, Spo13, which is known to regulate meiotic chromosome segregation will be studied to determine how it regulates this process and to identify its targets. Second, a genetic screen will be employed to identify new genes that regulate meiotic but not mitotic chromosome segregation.