The molecular events involved in the induction of petite yeast mutants by fluorinated pyrimidines. 1976

S G Oliver, and D H Williamson

The fluorinated pyrimidines 5-fluorouracil (5FU) and 5-fluorocytosine (5FC) induce the cytoplasmic petite mutation in the yeast Saccharomyces cerevisiae with high efficiency. It was found that in order to induce the mutation, 5FC must first be deaminated to 5FU. However, mutagenesis does not depend on the further conversion of 5FU to its deoxyriboside (5FUDR) and subsequent blockade of intracellular thymidine synthesis, since 5FUDR itself was found not to be mutagenic, and 5FU-induced mutagenesis was not antagonised by supplying thymidine monophosphate (dTMP) to a dTMP permeable strain. In any case, observations of the molecular changes accompanying petite induction in log phase cells ruled out the possibility that mutagenesis resulted simply from the dilution out of replication blocked mitDNA molecules, since the appearance of mutants coincided with the synthesis of altered mitDNA molecules. In different strains, the resulting defective molecules were either maintained, giving rise to suppressive rho- petites, or completely degraded, to give pure clones of neutral rho0 mutants. It is suggested that this degradative process was a conseuqence of the incorporation of 5FU into RNA.

UI MeSH Term Description Entries
D008928 Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed) Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D002500 Centrifugation, Isopycnic A technique used to separate particles according to their densities in a continuous density gradient. The sample is usually mixed with a solution of known gradient materials and subjected to centrifugation. Each particle sediments to the position at which the gradient density is equal to its own. The range of the density gradient is usually greater than that of the sample particles. It is used in purifying biological materials such as proteins, nucleic acids, organelles, and cell types. Isopycnic Centrifugation
D003596 Cytosine A pyrimidine base that is a fundamental unit of nucleic acids.
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D005111 Extrachromosomal Inheritance Vertical transmission of hereditary characters by DNA from cytoplasmic organelles such as MITOCHONDRIA; CHLOROPLASTS; and PLASTIDS, or from PLASMIDS or viral episomal DNA. Cytoplasmic Inheritance,Extranuclear Inheritance,Inheritance, Cytoplasmic,Inheritance, Extrachromosomal,Inheritance, Extranuclear
D005437 Flucytosine A fluorinated cytosine analog that is used as an antifungal agent. 5-Fluorocytosine,Alcobon,Ancobon,Ancotil
D005472 Fluorouracil A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid. 5-FU,5-FU Lederle,5-FU Medac,5-Fluorouracil,5-Fluorouracil-Biosyn,5-HU Hexal,5FU,Adrucil,Carac,Efudex,Efudix,Fluoro-Uracile ICN,Fluoroplex,Fluorouracil Mononitrate,Fluorouracil Monopotassium Salt,Fluorouracil Monosodium Salt,Fluorouracil Potassium Salt,Fluorouracil-GRY,Fluorouracile Dakota,Fluorouracilo Ferrer Far,Fluoruracil,Fluracedyl,Flurodex,Haemato-FU,Neofluor,Onkofluor,Ribofluor,5 FU Lederle,5 FU Medac,5 Fluorouracil,5 Fluorouracil Biosyn,5 HU Hexal,Dakota, Fluorouracile,Fluoro Uracile ICN,Fluorouracil GRY,Haemato FU
D005796 Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Cistron,Gene,Genetic Materials,Cistrons,Genetic Material,Material, Genetic,Materials, Genetic
D012441 Saccharomyces cerevisiae A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement. Baker's Yeast,Brewer's Yeast,Candida robusta,S. cerevisiae,Saccharomyces capensis,Saccharomyces italicus,Saccharomyces oviformis,Saccharomyces uvarum var. melibiosus,Yeast, Baker's,Yeast, Brewer's,Baker Yeast,S cerevisiae,Baker's Yeasts,Yeast, Baker

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