Analysis of the Generation and Segregation of Propagons: Entities That Propagate the [PSI+] Prion in Yeast

The propagation of the prion form of the yeast Sup35p protein, the so-called [PSI(+)] determinant, involves the generation and partition of a small number of particulate determinants that we propose calling "propagons." The numbers of propagons in [PSI(+)] cells can be inferred from the ki...

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Bibliographic Details
Published in:Genetics (Austin) 2003-09, Vol.165 (1), p.23-33
Main Authors: Cox, Brian, Ness, Frederique, Tuite, Mick
Format: Article
Language:English
Subjects:
Analysis
Cell culture
Chromosome Segregation
Gene Dosage
Genetics
Guanidine - metabolism
guanidine hydrochloride
Peptide Termination Factors
prion protein
Prions
Prions - genetics
Prions - metabolism
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
Sup35 gene
Sup35 protein
Yeast
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Summary:The propagation of the prion form of the yeast Sup35p protein, the so-called [PSI(+)] determinant, involves the generation and partition of a small number of particulate determinants that we propose calling "propagons." The numbers of propagons in [PSI(+)] cells can be inferred from the kinetics of elimination of [PSI(+)] during growth in the presence of a low concentration of guanidine hydrochloride (GdnHCl). Using this and an alternative method of counting the numbers of propagons, we demonstrate considerable clonal variation in the apparent numbers of propagons between different [PSI(+)] yeast strains, between different cultures of the same [PSI(+)] yeast strain, and between different cells of the same [PSI(+)] culture. We provide further evidence that propagon generation is blocked by growth in GdnHCl and that it is largely confined to the S phase of the cell cycle. In addition, we show that at low propagon number there is a bias toward retention of propagons in mother cells and that production of new propagons is very rapid when cells with depleted numbers of propagons are rescued into normal growth medium. The implications of our findings with respect to yeast prion propagation mechanisms are discussed.
ISSN:0016-6731
1943-2631
1943-2631
DOI:10.1093/genetics/165.1.23