ArticleGenetics2008
Lethal accumulation of guanylic nucleotides in Saccharomyces cerevisiae HPT1-deregulated mutants.
Article in Genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
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- Microtubule dynamics at low temperature: evidence that tubulin recycling limits assembly.Molecular biology of the cell · 2020Article
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- Bacillus subtilis 5'-nucleotidases with various functions and substrate specificities.BMC microbiology · 2016Article
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- Disruption of Nucleotide Homeostasis by the Antiproliferative Drug 5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside Monophosphate (AICAR).The Journal of biological chemistry · 2015Article
- Negative feedback-defective PRPS1 mutants drive thiopurine resistance in relapsed childhood ALL.Nature medicine · 2015Article
- Direct regulation of GTP homeostasis by (p)ppGpp: a critical component of viability and stress resistance.Molecular cell · 2012Article
- Functional significance of four successive glycine residues in the pyrophosphate binding loop of fungal 6-oxopurine phosphoribosyltransferases.Protein science : a publication of the Protein Society · 2012Article
- Dynamic metabolomics differentiates between carbon and energy starvation in recombinant Saccharomyces cerevisiae fermenting xylose.Biotechnology for biofuels · 2012Article
- Regulation of amino acid, nucleotide, and phosphate metabolism in Saccharomyces cerevisiae.Genetics · 2012Article
- Physiological and toxic effects of purine intermediate 5-amino-4-imidazolecarboxamide ribonucleotide (AICAR) in yeast.The Journal of biological chemistry · 2011Article
- Article
- Role of transmembrane domain 4 in ligand permeation by Crithidia fasciculata equilibrative nucleoside transporter 2 (CfNT2).The Journal of biological chemistry · 2010Article
- Control of ATP homeostasis during the respiro-fermentative transition in yeast.Molecular systems biology · 2010Article
- Article
- Metabolic intermediates selectively stimulate transcription factor interaction and modulate phosphate and purine pathways.Genes & development · 2009Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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