REGULATION OF THE MEIOTIC CELL CYCLE

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DESCRIPTION (provided by applicant): During the mitotic cell cycle a single round of DNA replication is followed by a chromosome segregation phase. Meiosis is a specialized cell cycle in which a single DNA replication phase is followed by two consecutive chromosome segregation phases. During the first meiotic division (meiosis I), homologous chromosomes are segregated whereas during the second meiotic division (meiosis II) sister chromatids are divided. 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. We propose to study two aspects of this unusual cell cycle. First, we will examine the transition between the first and the second meiotic division, during which conditions are established that facilitate a second round of chromosome segregation rather than DNA replication. Second, we will examine how the unusual meiosis I chromosome segregation pattern is established. To determine how the meiosis I - meiosis II transition is controlled we will characterize the function of the protein phosphatase Cdc14, which has been shown to control the analogous transition, the mitosis - G1 transition during the mitotic cell cycle. We will assess how Cdc14 controls the meiosis I - meiosis II transition and determine how Cdc14 is itself regulated during meiosis. Two approaches will be taken to characterize the events necessary to establish the meiosis I chromosome segregation pattern. (1) We will determine how Spo13, a protein known to regulate meiotic chromosome segregation, regulates this process. (2) We will characterize the role of genes we recently identified through a genetic screen, in establishing the meiosis I chromosome segregation. Chromosome mis-segregation during meiosis is a leading cause of birth defects and the leading cause of miscarriages in humans. It is, therefore, vital to understand the molecular mechanisms that regulate the meiotic cell cycle to open avenues towards the development of diagnostics and therapeutics.