title: Haploid yeast cells undergo a reversible phenotypic switch associated with chromosome II copy number.
abstract: SUP35 and SUP45 are essential genes encoding polypeptide chain release factors. However, mutants for these genes may be viable but display pleiotropic phenotypes which include, but are not limited to, nonsense suppressor phenotype due to translation termination defect. [PSI+] prion formation is another Sup35p-associated mechanism leading to nonsense suppression through decreased availability of functional Sup35p. [PSI+] differs from genuine sup35 mutations by the possibility of its elimination and subsequent re-induction. Some suppressor sup35 mutants had also been shown to undergo a reversible phenotypic switch in the opposite direction. This reversible switching had been attributed to a prion termed [ISP+]. However, even though many phenotypic and molecular level features of [ISP+] were revealed, the mechanism behind this phenomenon has not been clearly explained and might be more complex than suggested initially.
  
  
  
  Here we took a genomic approach to look into the molecular basis of the difference between the suppressor (Isp-) and non-suppressor (Isp+) phenotypes. We report that the reason for the difference between the Isp+and the Isp-phenotypes is chromosome II copy number changes and support our finding with showing that these changes are indeed reversible by reproducing the phenotypic switch and tracking karyotypic changes. Finally, we suggest mechanisms that mediate elevation in nonsense suppression efficiency upon amplification of chromosome II and facilitate switching between these states.
  
  
  
  (i) In our experimental system, amplification of chromosome II confers nonsense suppressor phenotype and guanidine hydrochloride resistance at the cost of overall decreased viability in rich medium. (ii) SFP1 might represent a novel regulator of chromosome stability, as SFP1 overexpression elevates frequency of the additional chromosome loss in our system. (iii) Prolonged treatment with guanidine hydrochloride leads to selection of resistant isolates, some of which are disomic for chromosome II.
authors.affiliation: Department of Genetics and Biotechnology, St. Petersburg State University, 199034, Universitetskaya nab. 7-9, St. Petersburg, Russia. p.drozdova@spbu.ru.
authors.forename: Polina
authors.initials: P
authors.lastname: Drozdova
authors.affiliation: Department of Genetics and Biotechnology, St. Petersburg State University, 199034, Universitetskaya nab. 7-9, St. Petersburg, Russia.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Mironova
authors.affiliation: Department of Genetics and Biotechnology, St. Petersburg State University, 199034, Universitetskaya nab. 7-9, St. Petersburg, Russia.|Laboratory of Amyloid Biology, St. Petersburg State University, 199034, Universitetskaya nab. 7-9, St. Petersburg, Russia.
authors.forename: Galina
authors.initials: G
authors.lastname: Zhouravleva
mesh_terms: D043171:Chromosomal Instability; D015825:Chromosomes, Fungal / Q000235:genetics* / Q000378:metabolism; D018389:Codon, Nonsense; D056915:DNA Copy Number Variations / Q000235:genetics*; D004271:DNA, Fungal / Q000032:analysis / Q000302:isolation & purification / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D019791:Guanidine / Q000494:pharmacology; D006238:Haploidy; D010454:Peptide Termination Factors / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D018389:Codon, Nonsense; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D010454:Peptide Termination Factors; C117421:SFP1 protein, S cerevisiae; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D019791:Guanidine
keywords: Aneuploidy; Chromosome instability; Nonsense suppression; SUP35; Translation termination; Yeast