Synaptonemal complex assembly and function in meiosis

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DESCRIPTION (provided by applicant): Meiosis is a specialized cell division process essential for sexual reproduction that unfolds in two phases (meiosis I and meiosis II) through which chromosome number is reduced by half generating haploid gametes. To segregate properly, chromosomes must undergo a series of steps that are unique to the first meiotic division, including (1) pairing with their homologous partners, (2) formation of a proteinaceous structure known as the synaptonemal complex (SC) along paired and aligned homologous chromosomes, and (3) completion of meiotic recombination leading to physical attachments (chiasmata) between homologs. Significantly, errors in any of these steps lead to chromosome nondisjunction, with disastrous consequences for the embryo. In humans, such events result in miscarriages and birth defects such as Down syndrome. Our focus is on investigating the roles and the macromolecular assembly of the SC, a structure at center stage during meiosis, whose functions are poorly understood and a matter of much debate despite its ubiquitous presence from yeast to mammals. Our studies are performed in the nematode C. elegans, a genetically amenable system in which abundant molecular and biochemical tools can be coupled with powerful cytological approaches. We have recently identified three critical SC components (SYP-1, SYP-2, and SYP-3). Beginning with the analysis of these components, we propose to address fundamental issues concerning the SC, including its assembly and disassembly, composition, and roles in homologous chromosome pairing, meiotic recombination, and chromosome segregation. We will do this by combining our cytological observations done in the context of an intact 3-D nuclear architecture in this system, with results from genetic and biochemical approaches, and a powerful genome-wide functional genomics screen involving RNA-mediated interference.