Studies of Synaptonemal Complex in C. elegans Meiosis

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A hallmark of cancerous cells is aneuploidy and a main source for errors in maintaining correct chromosome number are errors in chromosome redistribution upon cell division. Meiosis is a specialized form of cell division upon which chromosome number is reduced by half generating haploid gametes. In order to avoid errors in the redistribution of chromosomes during cell division, a series of mechanisms are utilized to regulate chromosomal segregation. One of the most important structures employed for this purpose is the synaptonemal complex (SC). This structure "zippers-up" pairs of homologous chromosomes maintaining them stably aligned with each other. Recombination is completed in the context of the fully formed SC. By identifying the components of the SC, how they interact among themselves, with the chromosomes and with the recombination machinery, we will be able to identify the errors that lead to increased nondisjunction and consequent disastrous outcomes such as miscarriages and birth defects. The goals through this fellowship are to: 1) Examine the participation of candidate SC components in the formation of the SC structure by: a- confirming a role in synapsis for these candidates through fluorescence in situ hybridization (FISH); b- performing localization of antibodies and GFP fusion proteins obtained for these candidates, in both, wild type and synapsis defective mutants; c- determining the extent of SC formation in the mutants via electron microscope (EM) analysis. 2) Identify new components required for synapsis by a two-hybrid screen. 3) Investigate the physical interactions among the putative SC components. 4) Assess the relationship between synapsis and meiotic recombination.