Previous Article | Next Article 
Molecular and Cellular Biology, December 2001, p. 7901-7912, Vol. 21, No. 23
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.23.7901-7912.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Yeast AMP Pathway Genes Respond to Adenine through
Regulated Synthesis of a Metabolic Intermediate
Karine
Rébora,
Christine
Desmoucelles,
Françoise
Borne,
Benoît
Pinson, and
Bertrand
Daignan-Fornier*
Institut de Biochimie et
Génétique Cellulaires, CNRS UMR 5095, 33077 Bordeaux Cedex,
France
Received 31 May 2001/Returned for modification 3 July 2001/Accepted 27 August 2001
In Saccharomyces cerevisiae, AMP biosynthesis genes
(ADE genes) are transcriptionally activated in the
absence of extracellular purines by the Bas1p and Bas2p (Pho2p)
transcription factors. We now show that expression of the
ADE genes is low in mutant strains affected in the first
seven steps of the pathway, while it is constitutively derepressed in
mutant strains affected in later steps. Combined with epistasy studies,
these results show that
5'-phosphoribosyl-4-succinocarboxamide-5-aminoimidazole (SAICAR), an
intermediate metabolite of the pathway, is needed for optimal activation of the ADE genes. Two-hybrid studies
establish that SAICAR is required to promote interaction between Bas1p
and Bas2p in vivo, while in vitro experiments suggest that the effect
of SAICAR on Bas1p-Bas2p interaction could be indirect. Importantly, feedback inhibition by ATP of Ade4p, catalyzing the first step of the
pathway, appears to regulate SAICAR synthesis in response to adenine
availability. Consistently, both ADE4 dominant mutations and overexpression of wild-type ADE4 lead to
deregulation of ADE gene expression. We conclude that
efficient transcription of yeast AMP biosynthesis genes requires
interaction between Bas1p and Bas2p which is promoted in the presence
of a metabolic intermediate whose synthesis is controlled by feedback
inhibition of Ade4p acting as the purine nucleotide sensor within the cell.
*
Corresponding author. Mailing address: Institut de
Biochimie et Génétique Cellulaires, CNRS UMR 5095, 1, rue
Camille Saint-Saëns, 33077 Bordeaux Cedex, France. Phone: (33) 5 56 99 90 55. Fax: (33) 5 56 99 90 59. E-mail: :
B.Daignan-Fornier{at}ibgc.u-bordeaux2.fr.
Molecular and Cellular Biology, December 2001, p. 7901-7912, Vol. 21, No. 23
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.23.7901-7912.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Saint-Marc, C., Pinson, B., Coulpier, F., Jourdren, L., Lisova, O., Daignan-Fornier, B.
(2009). Phenotypic Consequences of Purine Nucleotide Imbalance in Saccharomyces cerevisiae. Genetics
183: 529-538
[Abstract]
[Full Text]
-
Pinson, B., Vaur, S., Sagot, I., Coulpier, F., Lemoine, S., Daignan-Fornier, B.
(2009). Metabolic intermediates selectively stimulate transcription factor interaction and modulate phosphate and purine pathways. Genes Dev.
23: 1399-1407
[Abstract]
[Full Text]
-
Kowalski, D., Pendyala, L., Daignan-Fornier, B., Howell, S. B., Huang, R.-Y.
(2008). Dysregulation of Purine Nucleotide Biosynthesis Pathways Modulates Cisplatin Cytotoxicity in Saccharomyces cerevisiae. Mol. Pharmacol.
74: 1092-1100
[Abstract]
[Full Text]
-
Andersen, M. P., Nelson, Z. W., Hetrick, E. D., Gottschling, D. E.
(2008). A Genetic Screen for Increased Loss of Heterozygosity in Saccharomyces cerevisiae. Genetics
179: 1179-1195
[Abstract]
[Full Text]
-
Breton, A., Pinson, B., Coulpier, F., Giraud, M.-F., Dautant, A., Daignan-Fornier, B.
(2008). Lethal Accumulation of Guanylic Nucleotides in Saccharomyces cerevisiae HPT1-Deregulated Mutants. Genetics
178: 815-824
[Abstract]
[Full Text]
-
Philpott, C. C., Protchenko, O.
(2008). Response to Iron Deprivation in Saccharomyces cerevisiae. Eukaryot Cell
7: 20-27
[Full Text]
-
Koehler, R. N., Rachfall, N., Rolfes, R. J.
(2007). Activation of the ADE Genes Requires the Chromatin Remodeling Complexes SAGA and SWI/SNF. Eukaryot Cell
6: 1474-1485
[Abstract]
[Full Text]
-
Mateos, L., Jimenez, A., Revuelta, J. L., Santos, M. A.
(2006). Purine Biosynthesis, Riboflavin Production, and Trophic-Phase Span Are Controlled by a Myb-Related Transcription Factor in the Fungus Ashbya gossypii.. Appl. Environ. Microbiol.
72: 5052-5060
[Abstract]
[Full Text]
-
Mieczkowski, P. A., Dominska, M., Buck, M. J., Gerton, J. L., Lieb, J. D., Petes, T. D.
(2006). Global Analysis of the Relationship between the Binding of the Bas1p Transcription Factor and Meiosis-Specific Double-Strand DNA Breaks in Saccharomyces cerevisiae. Mol. Cell. Biol.
26: 1014-1027
[Abstract]
[Full Text]
-
Jimenez, A., Santos, M. A., Pompejus, M., Revuelta, J. L.
(2005). Metabolic Engineering of the Purine Pathway for Riboflavin Production in Ashbya gossypii. Appl. Environ. Microbiol.
71: 5743-5751
[Abstract]
[Full Text]
-
Som, I., Mitsch, R. N., Urbanowski, J. L., Rolfes, R. J.
(2005). DNA-Bound Bas1 Recruits Pho2 To Activate ADE Genes in Saccharomyces cerevisiae. Eukaryot Cell
4: 1725-1735
[Abstract]
[Full Text]
-
Todeschini, A.-L., Morillon, A., Springer, M., Lesage, P.
(2005). Severe Adenine Starvation Activates Ty1 Transcription and Retrotransposition in Saccharomyces cerevisiae. Mol. Cell. Biol.
25: 7459-7472
[Abstract]
[Full Text]
-
Rebora, K., Laloo, B., Daignan-Fornier, B.
(2005). Revisiting Purine-Histidine Cross-Pathway Regulation in Saccharomyces cerevisiae: A Central Role for a Small Molecule. Genetics
170: 61-70
[Abstract]
[Full Text]