Ploidy influences cellular responses to gross chromosomal rearrangements in saccharomyces cerevisiae

Abstract

BackgroundGross chromosomal rearrangements (GCRs) such as aneuploidy are key factors in genome evolution as well as being common features of human cancer. Their role in tumour initiation and progression has not yet been completely elucidated and the effects of additional chromosomes in cancer cells are still unknown. Most previous studies in which Saccharomyces cerevisiae has been used as a model for cancer cells have been carried out in the haploid context. To obtain new insights on the role of ploidy, the cellular effects of GCRs were compared between the haploid and diploid contexts.ResultsA total number of 21 haploid and diploid S. cerevisiae strains carrying various types of GCRs (aneuploidies, nonreciprocal translocations, segmental duplications and deletions) were studied with a view to determining the effects of ploidy on the cellular responses. Differences in colony and cell morphology as well as in the growth rates were observed between mutant and parental strains. These results suggest that cells are impaired physiologically in both contexts. We also investigated the variation in genomic expression in all the mutants. We observed that gene expression was significantly altered. The data obtained here clearly show that genes involved in energy metabolism, especially in the tricarboxylic acid cycle, are up-regulated in all these mutants. However, the genes involved in the composition of the ribosome or in RNA processing are down-regulated in diploids but up-regulated in haploids. Over-expression of genes involved in the regulation of the proteasome was found to occur only in haploid mutants.ConclusionThe present comparisons between the cellular responses of strains carrying GCRs in different ploidy contexts bring to light two main findings. First, GCRs induce a general stress response in all studied mutants, regardless of their ploidy. Secondly, the ploidy context plays a crucial role in maintaining the stoichiometric balance of the proteins: the translation rates decrease in diploid strains, whereas the excess protein synthesized is degraded in haploids by proteasome activity.

Global Changes in the Rat Heart Proteome Induced by Prolonged Morphine Treatment and Withdrawal

“…2). This finding is in agreement with some previous reports indicating a high proportion of metabolic proteins in the rat cardiac proteome [50]–[51]. Interestingly, both membrane fractions (PM and MT) contained approximately twice more transport proteins than the cytosolic fraction.…”

Disease‐associated patterns of disomic chromosomes in hyperhaploid neoplasms

“…The dramatic changes of the genome can be expected to affect gene and protein interactions as well as signaling within the cell. In yeast, ploidy status has been shown to influence gene expression, RNA processing, and protein turnover (Galitski et al, 1999;Torres et al, 2007;Jung et al, 2011); whether these findings in a single intact organism are relevant also in human somatic tumor cells that interact with other cells in a multicellular environment is, however, unknown.…”

New Insights into the Troubles of Aneuploidy

“…Oromendia, S. Dodgson, G. Brar, C. Gonzalez, J Weissman & A. Amon, unpublished data). Some aneuploids also have been shown to up-regulate genes involved in regulating proteasome activity (Jung et al 2011). In addition, evolution of disomic yeast strains identified several components of the proteasome pathway that were mutated in aneuploid strains evolved to exhibit increased proliferative abilities.…”