The major thrust of the proposed research to elucidate the regulation of a complex gene (Gart) for a purine biosynthetic pathway enzyme in Drosophila melanogaster. This gene encodes two polypeptides that arise by alternative processing of the primary transcript. Two immediate aims of the proposal are to understand why the transcript encoding metabolic functions is alternatively processed, and how that processing occurs at the molecular level. It is hypothesized that the processing allows for a single gene to provide multiple folate-utilizing enzyme activities for a cell cycle function (thymidine biosynthesis) as well as for the purine pathway. It will be necessary to determine the enzyme activities encoded by each transcript to test this hypothesis. Since post-transcriptional processing could be a common mechanism for the regulation of branching pathways, this proposal may be of general relevence to the control of metabolic enzymes. Another aim of this proposal is to understand how transcription of the gene is terminated. Both transcription termination and post-transcriptional processing will be investigated at the DNA sequence level using Drosophila germ-line transformation of sequences modified in vitro. A final specific aim of this proposal was suggested during a study in which the gene for this Drosophila purine pathway enzyme was fused to part of a yeast gene coding for a nuclear protein by recombinant DNA methods. The fusion product appeared to migrate to the nucleus, making possible a genetic analysis of nuclear transport in yeast.
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