RRC ID 11575
Author Rawls JM Jr.
Title Analysis of pyrimidine catabolism in Drosophila melanogaster using epistatic interactions with mutations of pyrimidine biosynthesis and beta-alanine metabolism.
Journal Genetics
Abstract The biochemical pathway for pyrimidine catabolism links the pathways for pyrimidine biosynthesis and salvage with beta-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; beta-alanine synthase (betaAS), 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 (r(Su(b))) of the dark cuticle phenotype of black mutants in which beta-alanine pools are diminished; these results confirm that pyrimidines are the major source of beta-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.
Volume 172(3)
Pages 1665-74
Published 2006-3
DOI 10.1534/genetics.105.052753
PII genetics.105.052753
PMID 16361227
PMC PMC1456268
MeSH Amidohydrolases / genetics* Amino Acid Sequence Amino Acid Substitution / genetics Animals Conserved Sequence Dihydrouracil Dehydrogenase (NADP) / genetics* Drosophila melanogaster / embryology Drosophila melanogaster / enzymology* Drosophila melanogaster / genetics Epistasis, Genetic* Female Fluorouracil / metabolism Humans Male Membrane Proteins / genetics Molecular Sequence Data Mutation* Phosphoproteins / genetics Pyrimidines / biosynthesis Pyrimidines / metabolism* Zonula Occludens-1 Protein beta-Alanine / genetics beta-Alanine / metabolism*
IF 4.075
Times Cited 14