RUI: Molecular and Genetic Analysis of Two Putative Rad51 Paralogs in Drosophila melanogaster

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Using sequence information gathered from the Drosophila Genome Project and Celera/Applied Biosystems, the Drosophila DNA Repair project has identified several paralogs of the yeast Rad51 gene. These paralogs are thought to promote Rad51-dependent strand exchange during the process of homologous recombinational repair (HRR) of DNA damage in cells. An analysis of hamster cell mutations, coupled with targeted knockout experiments in chicken cells, has shown that these genes play an important role in providing resistance to ionizing radiation and chemical mutagens. The focus of this research project is the study of DmRad51D and DmXRCC2 and their role in mitotic homologous recombination repair in fruit flies. The long-term goals include the use of genetic screens to identify other genes that interact with DmRad51D and DmXRCC2 in the process of HRR. The objectives of the research include 1) confirming the functional role of these putative D. melanogaster Rad51 paralogs by assaying functional knockouts in Drosophila culture cells, 2) examining the protein-protein interactions among these genes, 3) examining the expression pattern of these genes in flies, and 4) using P-element excision to generate loss of function mutations in the DmXRCC2 gene. DNA contains the instructions that allow cells to function correctly. However, DNA is constantly damaged by chemicals in cells and by radiation such as UV or gamma rays. Cells with damaged DNA do not always work properly and aberrations can result. A large group of genes repairs damaged DNA. This project focuses on the roles of two related genes in DNA repair. While scientists have some understanding of how these genes work in the test tube or in single cells, they still do not know much about how they work in a whole organism. This project will use molecular and genetic tools to study the role of these DNA repair genes in the fruit fly, where the activity of these genes can be studied in the entire animal. Almost all of the genes that fruit flies use during growth and development play an important role in all animals. This project will not only use the fruit fly to explore questions that are inherently interesting, but will also help to elucidate the function of related genes in other organisms, including humans.