Proteomic analysis of Mutator transposition

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DESCRIPTION (provided by applicant): Transposons are genetic elements that can move to new locations in the genome. They are ubiquitous in essentially all organisms, and recent genome sequencing projects in humans and maize have shown that transposons represent significant portions of both genomes. At the cellular level, transposon activity requires DNA and chromosomal repair processes to prevent cellular damage that could result in uncontrolled cell proliferation. Aside from these downstream studies on the consequences of transposon activity, relatively little is known about the proteins that modulate their upstream (excision and insertion) behavior in vivo. This study will use a proteomics-based approach to identify host proteins that regulate transposition behavior and potentially identify candidate proteins that modulate cell proliferation as well as establish a viable gene therapy alternative to viral vectors. The specific aims of this project are: (1) To compare the proteomes of tissues before and after activation of Mu; (2) to refine the spatial expression pattern of the transposition mechanisms; and (3) to mine genomic and cDNA databases to identify frame-shift translation candidate genes. The developmental role(s) of proteins associated with transposition in the four selected tissue types will be further analyzed using molecular, biochemical and reverse genetics approaches.