Warburg effect and translocation-induced genomic instability: two yeast models for cancer cells

Tosato, Valentina; GrĂ¼ning, Nana-Maria; Breitenbach, Michael; Arnak, Remigiusz; Ralser, Markus; Bruschi, Carlo V.
January 2013
Frontiers in Oncology;Jan2013, Vol. 3, p1
Academic Journal
Yeast has been established as an efficient model system to study biological principles underpinning human health. In this review we focus on yeast models covering two aspects of cancer formation and progression (i) the activity of pyruvate kinase (PK), which recapitulates metabolic features of cancer cells, including the Warburg effect, and (ii) chromosome bridge-induced translocation (BIT) mimiking genome instability in cancer. Saccharomyces cerevisiae is an excellent model to study cancer cell metabolism, as exponentially growing yeast cells exhibit many metabolic similarities with rapidly proliferating cancer cells. The metabolic reconfiguration includes an increase in glucose uptake and fermentation, at the expense of respiration and oxidative phosphorylation (the Warburg effect), and involves a broad reconfiguration of nucleotide and amino acid metabolism. Both in yeast and humans, the regulation of this process seems to have a central player, PK, which is up-regulated in cancer, and to occur mostly on a post-transcriptional and posttranslational basis. Furthermore, BIT allows to generate selectable translocation-derived recombinants ("translocants"), between any two desired chromosomal locations, in wild-type yeast strains transformed with a linear DNA cassette carrying a selectable marker flanked by two DNA sequences homologous to different chromosomes. Using the BIT system, targeted non-reciprocal translocations in mitosis are easily inducible. An extensive collection of different yeast translocants exhibiting genome instability and aberrant phenotypes similar to cancer cells has been produced and subjected to analysis. In this review, we hence provide an overview upon two yeast cancer models, and extrapolate general principles for mimicking human disease mechanisms in yeast.


Related Articles

  • Sequencing and comparison of yeast species to identify genes and regulatory elements. Kellis, Manolis; Patterson, Nick; Endrizzi, Matthew; Birren, Bruce; Lander, Eric S. // Nature;5/15/2003, Vol. 423 Issue 6937, p241 

    Identifying the functional elements encoded in a genome is one of the principal challenges in modern biology. Comparative genomics should offer a powerful, general approach. Here, we present a comparative analysis of the yeast Saccharomyces cerevisiae based on high-quality draft sequences of...

  • Novel mutations in the RAD3 and SSL1 genes perturb genome stability by stimulating recombination... Maines, Silvina; Negritto, M. Cristina // Genetics;Nov98, Vol. 150 Issue 3, p963 

    Presents evidence that the role played by the Saccharomyces cerevisiae RAD3 gene in short-repeat recombination control is distinct from its roles in ultraviolet light resistance and mutation avoidance. Stability of broken DNA molecules in rad3-G595R and SSL1-T242I single mutants;...

  • Genome engineering: Synthetic genome technology for yeast. Casci, Tanita // Nature Reviews Genetics;Nov2011, Vol. 12 Issue 11, p742 

    The article presents the constructed synthetic chromosome arm of the yeast Saccharomyces cerevisiae, for the creation of the synthetic eukaryotic genome.

  • Gene Copy-Number Variation in Haploid and Diploid Strains of the Yeast Saccharomyces cerevisiae. Hengshan Zhang; Zeidler, Ane F. B.; Wei Song; Puccia, Christopher M.; Malc, Ewa; Greenwell, Patricia W.; Mieczkowski, Piotr A.; Petes, Thomas D.; Argueso, Juan Lucas // Genetics;Mar2013, Vol. 193 Issue 3, p785 

    The increasing ability to sequence and compare multiple individual genomes within a species has highlighted the fact that copy-number variation (CNV) is a substantial and underappreciated source of genetic diversity. Chromosome-scale mutations occur at rates orders of magnitude higher than base...

  • A comprehensive strategy enabling high-resolution functional analysis of the yeast genome. Breslow, David K; Cameron, Dale M; Collins, Sean R; Schuldiner, Maya; Stewart-Ornstein, Jacob; Newman, Heather W.; Braun, Sigurd; Madhani, Hiten D.; Krogan, Nevan J.; Weissman, Jonathan S. // Nature Methods;Aug2008, Vol. 5 Issue 8, p711 

    Functional genomic studies in Saccharomyces cerevisiae have contributed enormously to our understanding of cellular processes. Their full potential, however, has been hampered by the limited availability of reagents to systematically study essential genes and the inability to quantify the small...

  • Increased glycolytic flux as an outcome of whole-genome duplication in yeast. Conant, Gavin C.; Wolfe, Kenneth H. // Molecular Systems Biology;2007, Vol. 3 Issue 1, p129 

    After whole-genome duplication (WGD), deletions return most loci to single copy. However, duplicate loci may survive through selection for increased dosage. Here, we show how the WGD increased copy number of some glycolytic genes could have conferred an almost immediate selective advantage to an...

  • The yeast proteome: say cheese! Ahmad, Sharon // Nature Reviews Molecular Cell Biology;Mar2006, Vol. 7 Issue 3, p155 

    Discusses research being done on a genome-wide screen for protein complexes and a characterization of the composition and organization of the cellular machinery of the yeast Saccharomyces cerevisiae. Reference to a study by Gavin and colleagues, published in the January 22, 2006 issue of...

  • Protection and replication of telomeres in fission yeast. Moser, Bettina A.; Nakamura, Toru M. // Biochemistry & Cell Biology;Oct2009, Vol. 87 Issue 5, p747 

    Telomeres, the natural ends of linear chromosomes, must be protected and completely replicated to guarantee genomic stability in eukaryotic cells. However, the protected state of telomeres is not compatible with recruitment of telomerase, an enzyme responsible for extending telomeric G-rich...

  • A Comprehensive Genome-Wide Map of Autonomously Replicating Sequences in a Naive Genome. Liachko, Ivan; Bhaskar, Anand; Chanmi Lee; Shau Chee Claire Chung; Bik-Kwoon Tye; Keich, Uri // PLoS Genetics;May2010, Vol. 6 Issue 5, p1 

    Eukaryotic chromosomes initiate DNA synthesis from multiple replication origins. The machinery that initiates DNA synthesis is highly conserved, but the sites where the replication initiation proteins bind have diverged significantly. Functional comparative genomics is an obvious approach to...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics