Our long-term goal is to understand how genetic recombination contributes to the faithful inheritance of chromosomes. Genetic recombination is of central importance to sexually reproducing organisms, since crossover recombination events between the DNA molecules of homologous chromosomes, and the resulting chiasmata, are necessary for proper chromosome segregation at the meiosis I division. Failure to form crossovers leads to chromosome missegregation and consequent aneuploidy, one of the leading causes of miscarriages and birth defects in humans. Most organisms make very few crossovers per chromosome pair (often one or two), indicating that the process must be tightly regulated to ensure that each pair will undergo at least one crossover per meiosis. Despite significant recent advances in understanding the mechanisms of meiotic recombination and the structural context in which it occurs, the mechanisms governing crossover regulation remain poorly understood. We propose to investigate the mechanisms of meiotic crossover control using the nematode C. elegans, a simple metazoan experimental system in which genetic, cytological and molecular tools for investigating meiosis are well established, and in which robust chromosome-wide regulation of crossing over has been demonstrated. We will test the hypothesis that structural integrity of the meiotic chromosome axes or the synaptonemal complex (SC) is required for this crossover control mechanism by investigating the effects of reducing function or abundance of known axis and SC components. We will use genetic and functional genomics approaches to identify components of the crossover control machinery, and use a battery of assays we developed to investigate how impairment of these components affects the organization and morphogenesis of meiotic chromosomes and the progress of meiotic recombination. We will investigate the role of the HIM-17 protein the initiation of recombination and in promoting the regulated formation of crossovers and functional chiasmata. Finally, we will investigate the roles of new components of the meiotic recombination machinery that we identify through the course of this work. ? ?
Showing the most recent 10 out of 23 publications
