title: Serine hydroxymethyltransferase: a key player connecting purine, folate and methionine metabolism in Saccharomyces cerevisiae.
abstract: Previous genetic analyses showed phenotypic interactions between 5-amino-4-imidazole carboxamide ribonucleotide 5'-phosphate (AICAR) produced from the purine and histidine pathways and methionine biosynthesis. Here, we revisited the effect of AICAR on methionine requirement due to AICAR accumulation in the presence of the fau1 mutation invalidating folinic acid remobilization. We found that this methionine auxotrophy could be suppressed by overexpression of the methionine synthase Met6 or by deletion of the serine hydroxymethyltransferase gene SHM2. We propose that in a fau1 background, AICAR, by stimulating the transcriptional expression of SHM2, leads to a folinic acid accumulation inhibiting methionine synthesis by Met6. In addition, we uncovered a new methionine auxotrophy for the ade3 bas1 double mutant that can be rescued by overexpressing the SHM2 gene. We propose that methionine auxotrophy in this mutant is the result of a competition for 5,10-methylenetetrahydrofolate between methionine and deoxythymidine monophosphate synthesis. Altogether, our data show intricate genetic interactions between one-carbon units, purine and methionine metabolism through fine-tuning of serine hydroxymethyltransferase by AICAR and the transcription factor Bas1.
authors.affiliation: UMR 5095, Institut de Biochimie et Génétique Cellulaires (IBGC), Université de Bordeaux, 1 rue Camille Saint-Saëns, 33077, Bordeaux, France.|UMR 5095, Institut de Biochimie et Génétique Cellulaires (IBGC), Centre National de la Recherche Scientifique (CNRS), 1 rue Camille Saint-Saëns CS 61390, 33077, Bordeaux, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Saint-Marc
authors.affiliation: UMR 5095, Institut de Biochimie et Génétique Cellulaires (IBGC), Université de Bordeaux, 1 rue Camille Saint-Saëns, 33077, Bordeaux, France.|UMR 5095, Institut de Biochimie et Génétique Cellulaires (IBGC), Centre National de la Recherche Scientifique (CNRS), 1 rue Camille Saint-Saëns CS 61390, 33077, Bordeaux, France.|Institut für Biologie, Martin-Luther Universität, Universität Halle-Wittenberg, Weinbergweg 10, 06120, Halle (Saale), Germany.
authors.forename: Hans C
authors.initials: HC
authors.lastname: Hürlimann
authors.affiliation: UMR 5095, Institut de Biochimie et Génétique Cellulaires (IBGC), Université de Bordeaux, 1 rue Camille Saint-Saëns, 33077, Bordeaux, France. b.daignan-fornier@ibgc.cnrs.fr.|UMR 5095, Institut de Biochimie et Génétique Cellulaires (IBGC), Centre National de la Recherche Scientifique (CNRS), 1 rue Camille Saint-Saëns CS 61390, 33077, Bordeaux, France. b.daignan-fornier@ibgc.cnrs.fr.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Daignan-Fornier
authors.affiliation: UMR 5095, Institut de Biochimie et Génétique Cellulaires (IBGC), Université de Bordeaux, 1 rue Camille Saint-Saëns, 33077, Bordeaux, France.|UMR 5095, Institut de Biochimie et Génétique Cellulaires (IBGC), Centre National de la Recherche Scientifique (CNRS), 1 rue Camille Saint-Saëns CS 61390, 33077, Bordeaux, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Pinson
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000378:metabolism; D019731:Carbon-Nitrogen Ligases / Q000235:genetics / Q000378:metabolism; D005492:Folic Acid / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D012696:Glycine Hydroxymethyltransferase / Q000235:genetics / Q000378:metabolism*; D006639:Histidine / Q000378:metabolism; D002955:Leucovorin / Q000378:metabolism; D008715:Methionine / Q000378:metabolism*; D009154:Mutation; D011687:Purines / Q000378:metabolism*; D012265:Ribonucleotides / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013763:Tetrahydrofolates / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: C061767:BAS1 protein, S cerevisiae; D011687:Purines; D012265:Ribonucleotides; D029701:Saccharomyces cerevisiae Proteins; D013763:Tetrahydrofolates; D015534:Trans-Activators; C013123:5,10-methylenetetrahydrofolic acid; D000620:Aminoimidazole Carboxamide; D006639:Histidine; D005492:Folic Acid; D008715:Methionine; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D012696:Glycine Hydroxymethyltransferase; D019731:Carbon-Nitrogen Ligases; C021557:5,10-methenyltetrahydrofolate synthetase; C031143:AICA ribonucleotide; D002955:Leucovorin; D013936:Thymidine
keywords: AICAR; Amino acids; Cross-pathway regulation; Nucleotides; One-carbon units; Serine hydroxymethyltransferase