Lethal accumulation of guanylic nucleotides in Saccharomyces cerevisiae HPT1-deregulated mutants
| Autor: | Fanny Coulpier, Benoît Pinson, Alain Dautant, Marie-France Giraud, Bertrand Daignan-Fornier, Annick Breton |
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| Přispěvatelé: | Grellety, Marie-Lise |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Hypoxanthine Phosphoribosyltransferase
Saccharomyces cerevisiae Proteins DNA damage Mutant Saccharomyces cerevisiae Guanosine Monophosphate Biology Investigations Polymerase Chain Reaction Gene Expression Regulation Fungal Genetics Extracellular Escherichia coli Nucleotide Mutation frequency [SDV.BC] Life Sciences [q-bio]/Cellular Biology ComputingMilieux_MISCELLANEOUS DNA Primers chemistry.chemical_classification biology.organism_classification Yeast Guanine Nucleotides chemistry Biochemistry Mutagenesis Mutation biology.protein Phosphoribosyltransferase Genes Lethal Plasmids |
| Popis: | Guanylic nucleotide biosynthesis is a conserved and highly regulated process. Drugs reducing GMP synthesis affect the immunological response and mutations enabling guanylic-derivative recycling lead to severe mental retardation. While the effects of decreased GMP synthesis have been well documented, the consequences of GMP overproduction in eukaryotes are poorly understood. In this work, we selected and characterized several mutations making yeast hypoxanthine–guanine phosphoribosyltransferase insensitive to feedback inhibition by GMP. In these mutants, accumulation of guanylic nucleotides can be triggered by addition of extracellular guanine. We show that such an accumulation is highly toxic for yeast cells and results in arrest of proliferation and massive cell death. This growth defect could be partially suppressed by overexpression of Rfx1p, a transcriptional repressor of the DNA damage response pathway. Importantly, neither guanylic nucleotide toxicity nor its suppression by Rfx1p was associated with an alteration of forward mutation frequency. |
| Databáze: | OpenAIRE |
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