Genetic and molecular dissection of meiotic silencing and unpaired DNA detection.

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DESCRIPTION (provided by applicant): Meiotic silencing is a phenomenon observed in animals and fungi whereby unpaired genes or other genetic elements are turned off during meiosis. The fact that it is triggered by unpaired DNA makes it ideally suited for the control of selfish genetic elements, such as viruses and transposons. Although meiotic silencing appears to be a type of RNA silencing - a generic term referring to small RNA mediated processes in eukaryotes - little else is known about its mechanistic nature. This proposal's primary goal is to investigate the unknown aspects of meiotic silencing, particularly the unpaired DMA detection process, using the eukaryotic organism in which it was initially discovered: Neurospora crassa. Specific aims to reach this goal include: 1) to develop and implement a high-throughput screen to identify meiotic silencing mutants 2) to identify and characterize the aberrant RNA transcripts theorized to be transcribed from unpaired meiotic DNA and 3) to clone and characterize alleles conferring resistance to [meiotic silencing-suppressing] meiotic drive elements. Relevance: Human selfish genetic elements have been linked to several genetic diseases. The research proposed herein seeks to elucidate the mechanism of meiotic silencing, a recently discovered biological process that may help defend the human genome from selfish genetic elements. Knowledge gained from this study could benefit future efforts towards the prevention of genetic disorders.