scholarly journals Yeast to Study Human Purine Metabolism Diseases

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 67 ◽  
Author(s):  
Bertrand Daignan-Fornier ◽  
Benoît Pinson
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Molecular Basis ◽  
Genetic Disorders ◽  
Relevant Information ◽  
Purine Metabolism ◽  
Model Organisms ◽  
Unicellular Organism ◽  
Purine Nucleotides ◽  
Yeast Saccharomyces Cerevisiae ◽  
Cellular Processes

Purine nucleotides are involved in a multitude of cellular processes, and the dysfunction of purine metabolism has drastic physiological and pathological consequences. Accordingly, several genetic disorders associated with defective purine metabolism have been reported. The etiology of these diseases is poorly understood and simple model organisms, such as yeast, have proved valuable to provide a more comprehensive view of the metabolic consequences caused by the identified mutations. In this review, we present results obtained with the yeast Saccharomyces cerevisiae to exemplify how a eukaryotic unicellular organism can offer highly relevant information for identifying the molecular basis of complex human diseases. Overall, purine metabolism illustrates a remarkable conservation of genes, functions and phenotypes between humans and yeast.

scholarly journals Molecular Basis of Fructose Utilization by the Wine Yeast Saccharomyces cerevisiae: a Mutated HXT3 Allele Enhances Fructose Fermentation

2007 ◽  
Vol 73 (8) ◽  
pp. 2432-2439 ◽  
Author(s):  
Carole Guillaume ◽  
Pierre Delobel ◽  
Jean-Marie Sablayrolles ◽  
Bruno Blondin
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Molecular Basis ◽  
Alcoholic Fermentation ◽  
Wine Yeast ◽  
Glycolytic Flux ◽  
Hexose Transporter ◽  
Wine Yeasts ◽  
Yeast Saccharomyces Cerevisiae ◽  
High Fructose ◽  
Fructose Fermentation

ABSTRACT Fructose utilization by wine yeasts is critically important for the maintenance of a high fermentation rate at the end of alcoholic fermentation. A Saccharomyces cerevisiae wine yeast able to ferment grape must sugars to dryness was found to have a high fructose utilization capacity. We investigated the molecular basis of this enhanced fructose utilization capacity by studying the properties of several hexose transporter (HXT) genes. We found that this wine yeast harbored a mutated HXT3 allele. A functional analysis of this mutated allele was performed by examining expression in an hxt1-7Δ strain. Expression of the mutated allele alone was found to be sufficient for producing an increase in fructose utilization during fermentation similar to that observed in the commercial wine yeast. This work provides the first demonstration that the pattern of fructose utilization during wine fermentation can be altered by expression of a mutated hexose transporter in a wine yeast. We also found that the glycolytic flux could be increased by overexpression of the mutant transporter gene, with no effect on fructose utilization. Our data demonstrate that the Hxt3 hexose transporter plays a key role in determining the glucose/fructose utilization ratio during fermentation.

Regulation of purine nucleotide biosynthesis: in yeast and beyond

2006 ◽  
Vol 34 (5) ◽  
pp. 786-790 ◽  
Author(s):  
R.J. Rolfes
Keyword(s):  
Saccharomyces Cerevisiae ◽  
De Novo ◽  
Purine Nucleotide ◽  
De Novo Synthesis ◽  
Normal Functioning ◽  
Purine Nucleotides ◽  
Yeast Saccharomyces Cerevisiae ◽  
Nucleotide Biosynthesis ◽  
Salvage Pathways ◽  
Pool Sizes

Purine nucleotides are critically important for the normal functioning of cells due to their myriad of activities. It is important for cells to maintain a balance in the pool sizes of the adenine-containing and guanine-containing nucleotides, which occurs by a combination of de novo synthesis and salvage pathways that interconvert the purine nucleotides. This review describes the mechanism for regulation of the biosynthetic genes in the yeast Saccharomyces cerevisiae and compares this mechanism with that described in several microbial species.

Signalling functions for sphingolipid long-chain bases in Saccharomyces cerevisiae

2005 ◽  
Vol 33 (5) ◽  
pp. 1170-1173 ◽  
Author(s):  
K. Liu ◽  
X. Zhang ◽  
C. Sumanasekera ◽  
R.L. Lester ◽  
R.C. Dickson
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein Kinase ◽  
Second Messengers ◽  
Dependent Protein Kinase ◽  
Yeast Saccharomyces Cerevisiae ◽  
Signalling Molecules ◽  
Cellular Processes ◽  
Wide Range ◽  
Dependent Protein ◽  
Long Chain

Over the past several years, studies of sphingolipid functions in the baker's yeast Saccharomyces cerevisiae have revealed that the sphingoid LCBs (long-chain bases), dihydrosphingosine and PHS (phytosphingosine), are important signalling molecules or second messengers under heat stress and during non-stressed conditions. LCBs are now recognized as regulators of AGC-type protein kinase (where AGC stands for protein kinases A, G and C) Pkh1 and Pkh2, which are homologues of mammalian phosphoinositide-dependent protein kinase 1. LCBs were previously shown to activate Pkh1 and Pkh2, which then activate the downstream protein kinase Pkc1. We have recently demonstrated that PHS stimulates Pkh1 to activate additional downstream kinases including Ypk1, Ypk2 and Sch9. We have also found that PHS acts downstream of Pkh1 and partially activates Ypk1, Ypk2 and Sch9. These kinases control a wide range of cellular processes including growth, cell wall integrity, stress resistance, endocytosis and aging. As we learn more about the cellular processes controlled by Ypk1, Ypk2 and Sch9, we will have a far greater appreciation of LCBs as second messengers.

scholarly journals Yeast as a Tool to Understand the Significance of Human Disease-Associated Gene Variants

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1303
Author(s):  
Tiziana Cervelli ◽  
Alvaro Galli
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Genetic Variability ◽  
Human Disease ◽  
Human Genetics ◽  
Model Organism ◽  
Model Organisms ◽  
Gene Variants ◽  
Yeast Saccharomyces Cerevisiae ◽  
Next Generation Dna Sequencing ◽  
Sequencing Technologies

At present, the great challenge in human genetics is to provide significance to the growing amount of human disease-associated gene variants identified by next generation DNA sequencing technologies. Increasing evidences suggest that model organisms are of pivotal importance to addressing this issue. Due to its genetic tractability, the yeast Saccharomyces cerevisiae represents a valuable model organism for understanding human genetic variability. In the present review, we show how S. cerevisiae has been used to study variants of genes involved in different diseases and in different pathways, highlighting the versatility of this model organism.

The CDC20 gene product of Saccharomyces cerevisiae, a beta-transducin homolog, is required for a subset of microtubule-dependent cellular processes

1991 ◽  
Vol 11 (11) ◽  
pp. 5592-5602
Author(s):  
N Sethi ◽  
M C Monteagudo ◽  
D Koshland ◽  
E Hogan ◽  
D J Burke
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Gene Product ◽  
Immunoblot Analysis ◽  
Restrictive Temperature ◽  
Wild Type ◽  
Yeast Saccharomyces Cerevisiae ◽  
Cellular Processes ◽  
Chromosome Separation ◽  
G1 Cells ◽  
Dependent Processes

Previous analysis of cdc20 mutants of the yeast Saccharomyces cerevisiae suggests that the CDC20 gene product (Cdc20p) is required for two microtubule-dependent processes, nuclear movements prior to anaphase and chromosome separation. Here we report that cdc20 mutants are defective for a third microtubule-mediated event, nuclear fusion during mating of G1 cells, but appear normal for a fourth microtubule-dependent process, nuclear migration after DNA replication. Therefore, Cdc20p is required for a subset of microtubule-dependent processes and functions at multiple stages in the life cycle. Consistent with this interpretation, we find that cdc20 cells arrested by alpha-factor or at the restrictive temperature accumulate anomalous microtubule structures, as detected by indirect immunofluorescence. The anomalous microtubule staining patterns are due to cdc20 because intragenic revertants that revert the temperature sensitivity have normal microtubule morphologies. cdc20 mutants have a sevenfold increase in the intensity of antitubulin fluorescence in intranuclear spindles compared with spindles from wild-type cells, yet the total amount of tubulin is indistinguishable by Western immunoblot analysis. This result suggests that Cdc20p modulates microtubule structure in wild-type cells either by promoting microtubule disassembly or by altering the surface of the microtubules. Finally, we cloned and sequenced CDC20 and show that it encodes a member of a family of proteins that share homology to the beta subunit of transducin.

scholarly journals Sequencing and functional analysis of the yeast genome.

1998 ◽  
Vol 45 (3) ◽  
pp. 627-643 ◽  
Author(s):  
M Zagulski ◽  
C J Herbert ◽  
J Rytka
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Eukaryotic Genome ◽  
Model Organisms ◽  
Yeast Genome ◽  
Entire Genome ◽  
Yeast Saccharomyces Cerevisiae ◽  
Entire Genome Sequence ◽  
Sequencing Project ◽  
New Genes ◽  
Public Data

The genome of the yeast Saccharomyces cerevisiae was sequenced by an international consortium of laboratories from Europe, Canada, the U.S.A. and Japan. This project is now finished and the complete sequence of the first eukaryotic genome was released to the public data bases in April 1996. An overview and preliminary analysis of the entire genome sequence was presented in a special issue of Nature in May 1997, entitled "The yeast genome directory". At its origin the Yeast Genome Sequencing Project provoked much debate and controversy; however, the final results obtained and the insights this has given us into the organisation and content of a eukaryotic genome have more than justified the expectations of the supporters of the project. The importance of genomic sequencing and analysis, especially of model organisms, is now widely accepted and this has resulted in the birth of the new science of genomics (Botstein & Cherry, 1997, Proc. Natl. Acad. Sci. U.S.A. 94, 5506). The information from gene and protein sequences ultimately lead to functional description of all genes. The main strategies describing possible ways to analyse the function of new genes that have been identified by systematic sequencing of Saccharomyces cerevisiae genome are described.

scholarly journals Mitochondrial Contact Site and Cristae Organizing System (MICOS) Machinery Supports Heme Biosynthesis by Enabling Optimal Performance of Ferrochelatase

2021 ◽  
Author(s):  
Jonathan V. Dietz ◽  
Mathilda M. Willoughby ◽  
Robert B. Piel ◽  
Teresa A. Ross ◽  
Iryna Bohovych ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Biosynthetic Pathway ◽  
Structural Features ◽  
Molecular Organization ◽  
Contact Site ◽  
Core Component ◽  
Yeast Saccharomyces Cerevisiae ◽  
Cytotoxic Effects ◽  
Cellular Processes ◽  
Biosynthetic Machinery

Heme is an essential cofactor required for a plethora of cellular processes in eukaryotes. In metazoans the heme biosynthetic pathway is typically partitioned between the cytosol and mitochondria, with the first and final steps taking place in the mitochondrion. The pathway has been extensively studied, and all the biosynthetic enzymes have been structurally characterized to varying extents. Nevertheless, our understanding of the regulation of heme synthesis and factors that influence this process in metazoans remains incomplete. Herein we investigate the molecular organization as well as the catalytic and structural features of the terminal pathway enzyme, ferrochelatase (Hem15), in the yeast Saccharomyces cerevisiae. Biochemical and genetic analyses reveal dynamic association of Hem15 with Mic60, a core component of the mitochondrial contact site and cristae organizing system (MICOS). Loss of MICOS negatively impacts Hem15 activity and results in accumulation of highly reactive and potentially toxic tetrapyrrole precursors that may result in oxidative damage. Restoring intermembrane connectivity in MICOS-deficient cells mitigates these cytotoxic effects. Our data provide new insights into how heme biosynthetic machinery is organized and regulated, linking mitochondrial architecture-organizing factors to heme homeostasis.

scholarly journals The CDC20 gene product of Saccharomyces cerevisiae, a beta-transducin homolog, is required for a subset of microtubule-dependent cellular processes.

1991 ◽  
Vol 11 (11) ◽  
pp. 5592-5602 ◽  
Author(s):  
N Sethi ◽  
M C Monteagudo ◽  
D Koshland ◽  
E Hogan ◽  
D J Burke
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Gene Product ◽  
Immunoblot Analysis ◽  
Restrictive Temperature ◽  
Wild Type ◽  
Yeast Saccharomyces Cerevisiae ◽  
Cellular Processes ◽  
Chromosome Separation ◽  
G1 Cells ◽  
Dependent Processes

Previous analysis of cdc20 mutants of the yeast Saccharomyces cerevisiae suggests that the CDC20 gene product (Cdc20p) is required for two microtubule-dependent processes, nuclear movements prior to anaphase and chromosome separation. Here we report that cdc20 mutants are defective for a third microtubule-mediated event, nuclear fusion during mating of G1 cells, but appear normal for a fourth microtubule-dependent process, nuclear migration after DNA replication. Therefore, Cdc20p is required for a subset of microtubule-dependent processes and functions at multiple stages in the life cycle. Consistent with this interpretation, we find that cdc20 cells arrested by alpha-factor or at the restrictive temperature accumulate anomalous microtubule structures, as detected by indirect immunofluorescence. The anomalous microtubule staining patterns are due to cdc20 because intragenic revertants that revert the temperature sensitivity have normal microtubule morphologies. cdc20 mutants have a sevenfold increase in the intensity of antitubulin fluorescence in intranuclear spindles compared with spindles from wild-type cells, yet the total amount of tubulin is indistinguishable by Western immunoblot analysis. This result suggests that Cdc20p modulates microtubule structure in wild-type cells either by promoting microtubule disassembly or by altering the surface of the microtubules. Finally, we cloned and sequenced CDC20 and show that it encodes a member of a family of proteins that share homology to the beta subunit of transducin.

scholarly journals Caenorhabditis elegans for rare disease modeling and drug discovery: strategies and strengths

2021 ◽  
Vol 14 (8) ◽  
Author(s):  
Peter A. Kropp ◽  
Rosemary Bauer ◽  
Isabella Zafra ◽  
Carina Graham ◽  
Andy Golden
Keyword(s):  
Caenorhabditis Elegans ◽  
Rare Disease ◽  
Rare Diseases ◽  
Disease Modeling ◽  
Relevant Information ◽  
Model Organisms ◽  
C Elegans ◽  
Cellular Processes ◽  
Ideal System ◽  
Small Model

ABSTRACT Although nearly 10% of Americans suffer from a rare disease, clinical progress in individual rare diseases is severely compromised by lack of attention and research resources compared to common diseases. It is thus imperative to investigate these diseases at their most basic level to build a foundation and provide the opportunity for understanding their mechanisms and phenotypes, as well as potential treatments. One strategy for effectively and efficiently studying rare diseases is using genetically tractable organisms to model the disease and learn about the essential cellular processes affected. Beyond investigating dysfunctional cellular processes, modeling rare diseases in simple organisms presents the opportunity to screen for pharmacological or genetic factors capable of ameliorating disease phenotypes. Among the small model organisms that excel in rare disease modeling is the nematode Caenorhabditis elegans. With a staggering breadth of research tools, C. elegans provides an ideal system in which to study human disease. Molecular and cellular processes can be easily elucidated, assayed and altered in ways that can be directly translated to humans. When paired with other model organisms and collaborative efforts with clinicians, the power of these C. elegans studies cannot be overstated. This Review highlights studies that have used C. elegans in diverse ways to understand rare diseases and aid in the development of treatments. With continuing and advancing technologies, the capabilities of this small round worm will continue to yield meaningful and clinically relevant information for human health.

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