title: The yeast prions [PSI+] and [URE3] are molecular degenerative diseases.
abstract: The yeast prions [URE3] and [PSI] are not found in wild strains, suggesting they are not an advantage. Prion-forming ability is not conserved, even within Saccharomyces, suggesting it is a disease. Prion domains have non-prion functions, explaining some conservation of sequence. However, in spite of the sequence being constrained in evolution by these non-prion functions, the prion domains vary more rapidly than the remainder of the molecule, and these changes produce a transmission barrier, suggesting that these changes were selected to block prion infection. Yeast prions [PSI] and [URE3] induce a cellular stress response (Hsp104 and Hsp70 induction), suggesting the cells are not happy about being infected. Recently, we showed that the array of [PSI] and [URE3] prions includes a majority of lethal or very toxic variants, a result not expected if either prion were an adaptive cellular response to stress.
authors: Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD, USA. wickner@helix.nih.gov
authors: Reed B
authors: RB
authors: Wickner
authors: Herman K
authors: HK
authors: Edskes
authors: David
authors: D
authors: Bateman
authors: Amy C
authors: AC
authors: Kelly
authors: Anton
authors: A
authors: Gorkovskiy
mesh_terms: D005979:Glutathione Peroxidase / Q000378:metabolism*; D008954:Models, Biological; D010454:Peptide Termination Factors / Q000378:metabolism*; D011328:Prions / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D013312:Stress, Physiological
chemical_list: D010454:Peptide Termination Factors; D011328:Prions; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D005979:Glutathione Peroxidase; C067020:URE2 protein, S cerevisiae