- THIS ARTICLE
- Full Text
- Full Text (PDF)
- Data Supplement
-
All Versions of this Article:
genetics.107.083295v1
178/2/815 most recent - Alert me when this article is cited
- Alert me if a correction is posted
- SERVICES
- Email this article to a friend
- Related articles in Genetics
- Similar articles in this journal
- Similar articles in PubMed
- Alert me to new issues of the journal
- Download to citation manager
- Reprints & Permissions
- CITING ARTICLES
- Citing Articles via HighWire
- Citing Articles via Google Scholar
- GOOGLE SCHOLAR
- Articles by Breton, A.
- Articles by Daignan-Fornier, B.
- Search for Related Content
- PUBMED
- PubMed Citation
- Articles by Breton, A.
- Articles by Daignan-Fornier, B.
Originally published as Genetics Published Articles Ahead of Print on February 3, 2008.
Genetics, Vol. 178, 815-824, February 2008, Copyright © 2008
doi:10.1534/genetics.107.083295
Lethal Accumulation of Guanylic Nucleotides in Saccharomyces cerevisiae HPT1-Deregulated Mutants
Annick Breton*,
,
Benoît Pinson*,,
Fanny Coulpier
,
Marie-France Giraud*,,
Alain Dautant*, and
Bertrand Daignan-Fornier*,,1
* Université Victor Segalen/Bordeaux 2, Institut de Biochimie et Génétique Cellulaires, 33077 Bordeaux, France, CNRS, UMR 5095, 33077 Bordeaux, France and IFR36, Plate-forme Transcriptome, École Normale Supérieure, 75230 Paris, France
1 Corresponding author: Institut de Biochimie et Génétique Cellulaires, CNRS UMR 5095 1, rue Camille Saint-Saëns, 33077 Bordeaux Cedex, France.
E-mail: b.daignan-fornier{at}ibgc.u-bordeaux2.fr
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.
Related articles in Genetics:
ISSUE HIGHLIGHTS
Genetics 2008 178: NP.
This article has been cited by other articles:
 |
|
 |
|
  B. Pinson, S. Vaur, I. Sagot, F. Coulpier, S. Lemoine, and B. Daignan-Fornier Metabolic intermediates selectively stimulate transcription factor interaction and modulate phosphate and purine pathways Genes & Dev., June 15, 2009; 23(12): 1399 - 1407. [Abstract] [Full Text] [PDF]
|
|