Analysis of Pyrimidine Catabolism in Drosophila melanogaster Using Epistatic Interactions With Mutations of Pyrimidine Biosynthesis and β-Alanine Metabolism
| Autor: | Jr. John M. Rawls |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Male
Mutant Molecular Sequence Data Biology Investigations medicine.disease_cause Conserved sequence Amidohydrolases Genetics medicine Dihydropyrimidine dehydrogenase Cuticle pigmentation Animals Humans Amino Acid Sequence Conserved Sequence Dihydrouracil Dehydrogenase (NADP) Mutation Catabolism Membrane Proteins Epistasis Genetic Phosphoproteins Drosophila melanogaster Pyrimidines Biochemistry Amino Acid Substitution Dihydropyrimidinase Pyrimidine metabolism Zonula Occludens-1 Protein beta-Alanine Female Fluorouracil |
| Popis: | The biochemical pathway for pyrimidine catabolism links the pathways for pyrimidine biosynthesis and salvage with β-alanine metabolism, providing an array of epistatic interactions with which to analyze mutations of these pathways. Loss-of-function mutations have been identified and characterized for each of the enzymes for pyrimidine catabolism: dihydropyrimidine dehydrogenase (DPD), su(r) mutants; dihydropyrimidinase (DHP), CRMP mutants; β-alanine synthase (βAS), pyd3 mutants. For all three genes, mutants are viable and fertile and manifest no obvious phenotypes, aside from a variety of epistatic interactions. Mutations of all three genes disrupt suppression by the rudimentary gain-of-function mutation (rSu(b)) of the dark cuticle phenotype of black mutants in which β-alanine pools are diminished; these results confirm that pyrimidines are the major source of β-alanine in cuticle pigmentation. The truncated wing phenotype of rudimentary mutants is suppressed completely by su(r) mutations and partially by CRMP mutations; however, no suppression is exhibited by pyd3 mutations. Similarly, su(r) mutants are hypersensitive to dietary 5-fluorouracil, CRMP mutants are less sensitive, and pyd3 mutants exhibit wild-type sensitivity. These results are discussed in the context of similar consequences of 5-fluoropyrimidine toxicity and pyrimidine catabolism mutations in humans. |
| Databáze: | OpenAIRE |
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