The pairing and synapsis of homologous chromosomes during meiosis is an early requirement for proper meiotic chromosome segregation. Defects in meiotic chromosome segregation generally cause the death of resulting progeny, but can also lead to serious developmental disorders, such as Down syndrome. How chromosomes identify, pair and ultimately synapse with their unique homolog is poorly understood. Genetic studies in C. elegans have implicated specific chromosomal regions at one end of each chromosome as potential pairing centers (PCs). I propose to investigate PC function by undertaking an RNA interference screen in a sensitized genetic background to identify genes required for PC activity. In addition to this genetic screen, I will identify meiotic chromosomal proteins proteomically by comparing the protein profiles of nuclei isolated from wildtype worms and mutant worms that lack a germline. Molecular factors identified by these complementary approaches will be further characterized to determine their roles in homolog pairing and synapsis.
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