Genetic and Physiological Aspects of Resistance to 5-Fluoropyrimidines in Saccharomyces cerevisiae
- 1 June 1970
- journal article
- Published by American Society for Microbiology in Journal of Bacteriology
- Vol. 102 (3), 607-15
- https://doi.org/10.1128/jb.102.3.607-615.1970
Abstract
Mutants resistant to 5-fluorouracil, 5-fluorocytosine, and 5-fluorouridine were selected in yeast, and the mechanisms of their resistance were investigated. The investigated mutations map in seven different loci. (i) A mutation at the locus FUI 1 gives specifically resistance to 5-fluorouridine. (ii) Two loci are involved in a specific 5-fluorocytosine resistance: a mutation at locus FCY 1 produces a loss of cytosine deaminase activity; a mutation at locus FCY 2 results in the loss of the activity of a cytosine-specific permease. (iii) A mutation at the locus FUR 4 gives a simultaneous resistance to 5-fluorouracil and to 5-fluorouridine by loss in the activity of the uracil-specific permease. (iv) We found three types of mutants in the locus FUR 1. One is dominant and weakly resistant to 5-fluorouracil, 5-fluorocytosine, and 5-fluorouridine. The two others are recessive and are unable to catalyze one of the steps involved in uracil transformation into uridine 5'-monophosphate; this block-age explains their strong resistance to 5-fluorouracil and 5-fluorocytosine. Of these two mutants, one is resistant to 5-fluorouridine and the other is not. (v) Mutations at locus FUR 2 give resistance to 5-fluorouracil, 5-fluorocytosine, and 5-fluorouridine. These mutations are dominant and lead to a loss in the feedback regulation of the aspartic transcarbamylase activity by uridine triphosphate. (vi) The mutants FUR 3 are resistant to 5-fluorocytosine and 5-fluorouridine. They are dominant and physiologically related to the mutants of the locus FUR 1 but their mechanism of resistance is not understood.Keywords
This publication has 20 references indexed in Scilit:
- The Utilization of Exogenous Pyrimidines and the Recycling of Uridine‐5′‐Phosphate Derivatives in Saccharomyces cerevisiae, as Studied by Means of Mutants Affected in Pyrimidine Uptake and MetabolismEuropean Journal of Biochemistry, 1969
- The Control of Nucleotide BiosynthesisAnnual Review of Biochemistry, 1968
- Thin-layer chromatography of nucleotides, nucleosides and nucleic acid basesBiochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis, 1965
- Biochemical Mechanisms of Drug ResistanceAnnual Review of Microbiology, 1964
- Studies on the acid-soluble nucleotide pool in thymine-requiring mutants of Escherichia coli during thymine starvationBiochimica et Biophysica Acta (BBA) - Specialized Section on Nucleic Acids and Related Subjects, 1964
- Biochemistry of Cancer (Metabolic Aspects)Annual Review of Biochemistry, 1963
- Enzymes of uracil metabolism in the Ehrlich ascites tumour and mammalian liverBiochimica et Biophysica Acta, 1958
- Formation of Uridine Phosphates from Uracil in Extracts of Ehrlich Ascites Tumor.Acta Chemica Scandinavica, 1957
- On the Cytosine Deaminase of Yeast1Journal of the American Chemical Society, 1952
- Partial Purification of a Non-phosphorylytic Uridine Nucleosidase from YeastJournal of the American Chemical Society, 1951