A5088388229- Fungal and yeast genetics research
- Biochemical and Molecular Research
- Polyamine Metabolism and Applications
- RNA and protein synthesis mechanisms
- Microbial Metabolic Engineering and Bioproduction
- Genomics and Chromatin Dynamics
- Adenosine and Purinergic Signaling
- RNA modifications and cancer
- Mitochondrial Function and Pathology
- HIV/AIDS drug development and treatment
- Calcium signaling and nucleotide metabolism
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- Plant nutrient uptake and metabolism
- Cytomegalovirus and herpesvirus research
- DNA Repair Mechanisms
- Metabolism, Diabetes, and Cancer
- Endoplasmic Reticulum Stress and Disease
- Amino Acid Enzymes and Metabolism
- Sirtuins and Resveratrol in Medicine
- Porphyrin Metabolism and Disorders
- Biotin and Related Studies
- Genetics, Aging, and Longevity in Model Organisms
- Microtubule and mitosis dynamics
- Cellular Mechanics and Interactions
Institut de Biochimie et Génétique Cellulaires
2012-2024
Université de Bordeaux
2012-2024
Centre National de la Recherche Scientifique
2011-2024
Centre National pour la Recherche Scientifique et Technique (CNRST)
2015-2019
École Normale Supérieure - PSL
2012
Hôpital Rangueil
2010
Université Toulouse III - Paul Sabatier
2007-2010
Roswell Park Comprehensive Cancer Center
2006-2008
Université Paris-Sud
1987-1997
Gembloux Agro-Bio Tech
1997
Abstract Ever since the beginning of biochemical analysis, yeast has been a pioneering model for studying regulation eukaryotic metabolism. During last three decades, combination powerful genetics and genome-wide approaches led to more integrated view metabolic regulation. Multiple layers regulation, from suprapathway control individual gene responses, have discovered. Constitutive dedicated systems that are critical in sensing intra- extracellular environment identified, there is growing...
The 26S proteasome is responsible for the controlled proteolysis of a vast number proteins, including crucial cell cycle regulators. Accordingly, in Saccharomyces cerevisiae, function mandatory progression. In budding yeast, assembled nucleus, where it localized throughout cycle. We report that upon entry into quiescence, subunits massively relocalize from nucleus motile cytoplasmic structures. further demonstrate these structures are reservoirs rapidly mobilized exit quiescence. Therefore,...
We have found cross-pathway regulation between purine and histidine biosynthesis in yeast. The transcription factors BAS1 BAS2/PHO2, which are also regulators of the pathway, participate biosynthetic pathway. Analysis four genes pathway (ADE1, ADE2, ADE5,7, ADE8) shows that their expression is repressed by adenine. maximal basal induced these requires presence both BAS2. factor has been shown to bind at a site containing TGACTC hexanucleotide motif ADE2 ADE5,7 promoters. This required for...
Quiescence is defined as a temporary arrest of proliferation, yet it likely encompasses various cellular situations. Our knowledge about this widespread state remains limited. In particular, little known the molecular determinants that orchestrate quiescence establishment and exit. Here we show upon carbon source exhaustion, budding yeast can enter from all cell cycle phases. Moreover, using structures are candidate markers for quiescence, found first steps exit be triggered independently...
Cancers rely on multiple, heterogeneous processes at different scales, pertaining to many biomedical fields. Therefore, understanding cancer is necessarily an interdisciplinary task that requires placing specialised experimental and clinical research into a broader conceptual, theoretical, methodological framework. Without such framework, oncology will collect piecemeal results, with scant dialogue between the scientific communities studying cancer. We argue one important way forward in...
Because some metabolic intermediates are involved in more than one pathway, crosstalk between pathways is crucial to maintaining homeostasis. AMP and histidine biosynthesis coregulated at the transcriptional level response adenine availability. 5'-Phosphoribosyl-4-carboxamide-5-aminoimidazole (AICAR), a intermediate crossroads these two pathways, shown here be critical for activation of absence adenine. In this study, we show that both significantly contribute AICAR synthesis. Furthermore,...
Most eukaryotic cells spend most of their life in a quiescent state, poised to respond specific signals proliferate. In Saccharomyces cerevisiae, entry into and exit from quiescence are dependent only on the availability nutrients environment. The transition proliferation requires not drastic metabolic changes but also complete remodeling various cellular structures. Here, we describe an actin cytoskeleton organization yeast state. When cease divide, is reorganized structures that named...
Cells use strategic metabolites to sense the metabolome and accordingly modulate gene expression. Here, we show that purine phosphate pathways are positively regulated by metabolic intermediate AICAR (5′-phosphoribosyl-5-amino-4-imidazole carboxamide). The transcription factor Pho2p is required for up-regulation of all AICAR-responsive genes. Accordingly, binding pathway promoters enhanced upon accumulation. In vitro, binds both Pho4p factors stimulates interaction between either Bas1p or in...
The immunosuppressive drug mycophenolic acid (MPA) is a potent and specific inhibitor of IMP dehydrogenase, the first committed step GMP synthesis. A screen for yeast genes affecting MPA sensitivity, when overexpressed, allowed us to identify two genes, IMD2 TPO1, encoding homologue dehydrogenase vacuolar pump, respectively. In parallel, 4787 strains, each carrying an identified knock-out mutation, were tested growth in presence MPA, allowing identification 100 new resistance disrupted....
In Saccharomyces cerevisiae, AMP biosynthesis genes (ADE genes) are transcriptionally activated in the absence of extracellular purines by Bas1p and Bas2p (Pho2p) transcription factors.We now show that expression ADE is low mutant strains affected first seven steps pathway, while it constitutively derepressed later steps.Combined with epistasy studies, these results 5-phosphoribosyl-4-succinocarboxamide-5-aminoimidazole (SAICAR), an intermediate metabolite needed for optimal activation...
The effect of extracellular adenine and the role transcriptional activator Bas1p on expression yeast genome was assessed by two‐dimensional (2D) analysis proteome. These data combined with LacZ fusions northern blot allow us to show that synthesis enzymes for all 10 steps involved in purine de novo is repressed presence requires BAS1 BAS2 optimal expression. We also ADE12 ADE13 , two genes required AMP from inosine 5′monophosphate (IMP), co‐regulated pathway genes. same approach, used study...
Mitochondrial biogenesis is a complex process. It necessitates the participation of both nuclear and mitochondrial genomes. This process highly regulated, content within cell varies according to energy demand. In yeast Saccharomyces cerevisiae, cAMP pathway involved in regulation biogenesis. An overactivation this leads an increase enzymatic content. Of three protein kinases, we have previously shown that Tpk3p one paper, investigated molecular mechanisms govern We show absence Tpk3p,...
AICAR (5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranosyl 5'-monophosphate) is a natural metabolic intermediate of purine biosynthesis that present in all organisms. In yeast, plays important regulatory roles under physiological conditions, notably through its direct interactions with transcription factors. humans, accumulates several diseases, but contribution to the symptoms has not yet been elucidated. Further, highly promising properties which have recently revealed. Indeed, it...
Lesch-Nyhan disease is a rare X-linked neurodevelopemental metabolic disorder caused by wide variety of mutations in the HPRT1 gene leading to deficiency purine recycling enzyme hypoxanthine-guanine phosphoribosyltransferase (HGprt). The residual HGprt activity correlates with various phenotypes (LN) patients and particular different degree neurobehavioral disturbances. prevalence this considered be underestimated due large heterogeneity its clinical symptoms difficulty diagnosing less...
Metabolism is a highly integrated process resulting in energy and biomass production. While individual metabolic routes are well characterized, the mechanisms ensuring crosstalk between pathways poorly described, although they crucial for homeostasis. Here, we establish co-regulation of purine pyridine metabolism response to external adenine through two separable mechanisms. First, depletion promotes transcriptional upregulation de novo NAD+ biosynthesis genes by mechanism requiring...
Sequencing of the Saccharomyces cerevisiae genome revealed an open reading frame (YJR105w) encoding a putative protein highly similar to adenosine kinases from other species. Disruption this gene (renamed ADO1) affected utilization S-adenosyl methionine (AdoMet) as purine source and resulted in severe reduction kinase activity crude extracts. Furthermore, knock-out ADO1 led excretion medium resistance toxic analogue cordycepin. From these data we conclude that encodes yeast kinase. We also...
Phosphate is an essential nutrient that must be taken up from the growth medium through specific transporters. In Saccharomyces cerevisiae, both high and low affinity orthophosphate carriers allow this micro-organism to cope with environmental variations. Intriguingly, in study we found a tight correlation between selenite resistance expression of carrier Pho84p. Our work further revealed mutations genes (PHO87, PHO90, PHO91) cause deregulation phosphate-repressed genes. Strikingly, due...
Using an expression library, we have isolated yeast genes activated in the presence of CCAAT box-binding protein HAP2. One these genes, SDH3, encodes cytochrome b560 subunit respiratory complex II. The SDH3 contains three potential transmembrane domains and is more than 30% identical to bovine a mitochondrially encoded from Marchantia polymorpha. Disruption shows that this gene required for growth on non-fermentable carbon sources. Expression SDH1, SDH4 HAP2 transcriptional activator.
Summary Adenylate kinase (Adk1p) is a pivotal enzyme in both energetic and adenylic nucleotide metabolisms. In this paper, using transcriptomic analysis, we show that the lack of Adk1p strongly induced expression PHO ADE genes involved phosphate utilization AMP de novo biosynthesis respectively. Isolation characterization adk1 point mutants affecting PHO5 revealed all these mutations also severely affected catalytic activity, as well PHO84 ADE1 transcription. Furthermore, overexpression...
Recent studies associating dietary selenium with reduced cancer susceptibility have aroused interest in this substance. In the millimolar range, selenite is toxic and slightly mutagenic for yeast. We show that selenite‐treated yeast cells tend to arrest as large budded abolished a rad9 mutant significantly sensitive selenite. Interestingly, rev3 affected error‐prone repair pathway also selenite, whereas mutations other DNA pathways do not strongly affect resistance propose treatment leads...
In response to an external source of adenine, yeast cells repress the expression purine biosynthesis pathway genes. To identify necessary components this signalling mechanism, we have isolated mutants that are constitutively active for expression. These were named bra (for bypass repression by adenine). BRA7 is allelic FCY2, gene encoding cytosine permease and BRA9 ADE12, adenylosuccinate synthetase. BRA6 BRA1 new genes encoding, respectively, hypoxanthine guanine phosphoribosyl transferase...
In Saccharomyces cerevisiae, carbon and nitrogen metabolisms are connected via the incorporation of ammonia into glutamate; this reaction is catalyzed by NADP-dependent glutamate dehydrogenase (NADP-GDH) encoded GDH1 gene. report, we show that gene requires CCAAT box-binding activator (HAP complex) for optimal expression. This conclusion based on several lines evidence: (1) overexpression can correct growth defect hap2 hap3 mutants ammonium sulfate as a source, (ii) Northern (RNA) blot...