title: Ploidy controls [URE3] prion propagation in yeast.
abstract: Previous genetic approaches have enabled the identification of key partners for prion propagation in yeast, such as HSP104. All the experiments performed thus far have been conducted in a haploid context. In this study, we used a diploid yeast strain to identify genes that interfere with [URE3] stability. Our screen, based on a multi-copy library, revealed an unsuspected role for centromeric sequences that appear to decrease the mitotic stability of this prion. Because an increase in centromeric sequences interferes with [URE3] transmission, we analyzed this property in tetraploid yeast cells. We found that in such strains, [URE3] is quite unstable, with the concentration of Hsp104p being a key factor for the stabilization of [URE3] in 4n yeast cells. We also showed that HSP104 stabilization can occur independently of its 'disaggregate' activity. These results may explain the discrepancy between wild strains bearing or not bearing prions because they differ in their ploidy. These results provide new insight into prion biology by linking the control of ploidy to protein misfolding and demonstrate that [URE3] is also a gain-of-function phenotype.
authors.affiliation: IBMM CP300, Université Libre de Bruxelles (ULB), Gosselies, Belgique.
authors.forename: Myriam
authors.initials: M
authors.lastname: Crapeau
authors.forename: Laurent
authors.initials: L
authors.lastname: Maillet
authors.forename: Christophe
authors.initials: C
authors.lastname: Cullin
mesh_terms: D002503:Centromere; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D011003:Ploidies; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D015003:Yeasts / Q000235:genetics* / Q000378:metabolism*
chemical_list: D006360:Heat-Shock Proteins; D011328:Prions; D029701:Saccharomyces cerevisiae Proteins; D005979:Glutathione Peroxidase; C067020:URE2 protein, S cerevisiae
keywords: HSP104; amyloid; ploidy; prion; yeast