title: Aneuploidy causes proteotoxic stress in yeast.
abstract: Gains or losses of entire chromosomes lead to aneuploidy, a condition tolerated poorly in all eukaryotes analyzed to date. How aneuploidy affects organismal and cellular physiology is poorly understood. We found that aneuploid budding yeast cells are under proteotoxic stress. Aneuploid strains are prone to aggregation of endogenous proteins as well as of ectopically expressed hard-to-fold proteins such as those containing polyglutamine (polyQ) stretches. Protein aggregate formation in aneuploid yeast strains is likely due to limiting protein quality-control systems, since the proteasome and at least one chaperone family, Hsp90, are compromised in many aneuploid strains. The link between aneuploidy and the formation and persistence of protein aggregates could have important implications for diseases such as cancer and neurodegeneration.
authors.affiliation: Koch Institute for Integrative Cancer Research, Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02138, USA.
authors.forename: Ana B
authors.initials: AB
authors.lastname: Oromendia
authors.forename: Stacie E
authors.initials: SE
authors.lastname: Dodgson
authors.forename: Angelika
authors.initials: A
authors.lastname: Amon
mesh_terms: D000782:Aneuploidy; D020090:Chromosome Segregation; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D000071058:Huntingtin Protein; D008540:Meiosis / Q000235:genetics; D008938:Mitosis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017510:Protein Folding; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000378:metabolism
chemical_list: C074510:HSP82 protein, S cerevisiae; D018841:HSP90 Heat-Shock Proteins; C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D029701:Saccharomyces cerevisiae Proteins; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D010450:Endopeptidases; D046988:Proteasome Endopeptidase Complex; C109028:UBP6 protein, S cerevisiae