Science · 2007 · 1K citations · 23 references
Life SciencesCell BiologyGeneticsCell CycleCell DivisionCell ProliferationAneuploidyChromosome DoublingMitosisYeast GeneticsAneuploidy EffectsCell Division ControlProtein ProductionYeast AneuploidyYeast Polyploidy
Aneuploidy, common in tumor cells, has an unclear impact on cellular physiology. The authors generated a library of haploid yeast strains, each carrying an extra copy of nearly every yeast chromosome. Aneuploid yeast strains exhibit cell cycle defects, heightened glucose uptake, and sensitivity to protein synthesis stress, all linked to excess protein production, and these phenotypes confer a proliferative disadvantage regardless of which chromosome is duplicated.
Aneuploidy is a condition frequently found in tumor cells, but its effect on cellular physiology is not known. We have characterized one aspect of aneuploidy: the gain of extra chromosomes. We created a collection of haploid yeast strains that each bear an extra copy of one or more of almost all of the yeast chromosomes. Their characterization revealed that aneuploid strains share a number of phenotypes, including defects in cell cycle progression, increased glucose uptake, and increased sensitivity to conditions interfering with protein synthesis and protein folding. These phenotypes were observed only in strains carrying additional yeast genes, which indicates that they reflect the consequences of additional protein production as well as the resulting imbalances in cellular protein composition. We conclude that aneuploidy causes not only a proliferative disadvantage but also a set of phenotypes that is independent of the identity of the individual extra chromosomes.
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Elizabeth I. Boyle, Shuai Weng, Jeremy Gollub et al. · Bioinformatics · 2004 · 2.2K citations · Full text
Rapid degradation of a large fraction of newly synthesized proteins by proteasomes
Ulrich S. Schubert, Luis C. Antón, James S. Gibbs et al. · Nature · 2000 · 1.5K citations
SEGMENTAL ANEUPLOIDY AND THE GENETIC GROSS STRUCTURE OF THE DROSOPHILA GENOME
Dan L. Lindsley, L Sandler, Bruce S. Baker et al. · Genetics · 1972 · 611 citations · Full text