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doi:10.1534/genetics.104.039396
A more recent version of this article appeared on May 1, 2005.
REGULAR RESEARCH PAPERS |
Revisiting purine-histidine cross-pathway regulation in Saccharomyces cerevisiae : a central role for a small molecule
Karine Rébora 1, Benoît Laloo 1 and Bertrand Daignan-Fornier 2*
1 IBGC CNRS Université Bordeaux2
2 Institut de Biochimie et Genetique Cellulaires
* To whom correspondence should be addressed. E-mail: b.daignan-fornier{at}ibgc.u-bordeaux2.fr.
Submitted on December 6, 2004
Revised on December 20, 2004
Accepted on 20 December 2004
Because some metabolic intermediates are involved in more than one pathway, crosstalk between pathways is crucial to maintain homeostasis. AMP and histidine biosynthesis pathways are coregulated at the transcriptional level in response to adenine availability. 5'-phosphoribosyl-4-carboxamide-5-aminoimidazole (AICAR), a metabolic intermediate at the crossroads between these two pathways, is shown here to be critical for activation of the transcriptional response in the absence of adenine. In this study, we show that both AMP and histidine pathways significantly contribute to AICAR synthesis. Furthermore, we show that up-regulation of the histidine pathway clearly interferes with regulation of the AMP pathway, providing thus an explanation for the regulatory crosstalk between these pathways. Finally, we revisit the histidine auxotrophy of ade3 or ade16 ade17 mutants. Interestingly, overexpression of PMU1, encoding a potential phosphomutase, partially suppresses histidine requirement of an ade3 ade16 ade17 triple mutant, most probably by reducing the level of AICAR in this mutant. Together our data clearly establish that AICAR is not just a metabolic intermediate but also acts as a true regulatory molecule.
Key Words: AICAR, cerevisiae, cros-pathway regulation, histidine, purine
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