We propose to isolate and characterize the chinese hamster and human genes for a number of enzymes of purine and pyrimidine nucleotide synthesis, including the gene coding for CAD, the multifunctional protein encoding the first three enzymes of UMP synthesis, UMPS, the protein carrying the last two enzymes of UMP synthesis, and at least two of the genes coding for enzymes of purine synthesis, GART, which probably encodes a protein carrying three of the first five enzymes of this pathway, and FGARAT, which encodes at least one and perhaps two of these. We will compare the structures of these genes for common features which may define regulatory elements and use nucleic acid probes to study regulation of these pathways in defective mutant (auxotrophs), gene emplified cell lines, and wild-type in a variety of experimental conditions and to examine the genes in the mutants for alterations. We propose to examine the feasibility of extending these studies into a whole animal system in which mutant animals exist, Drosophila melanogaster, in order to study directly the role of these genes in animal development. Finally, we propose to continue our studies on chromosomal translocations associated with malignancy and to investigate whether these studies can be extended to an animal (rat model system).
