Guanidine hydrochloride blocks a critical step in the propagation of the prion-like determinant [PSI+] of Saccharomyces cerevisiae

Eaglestone, S.S. and Ruddock, L.W and Cox, B.S and Tuite, M.F. (2000) Guanidine hydrochloride blocks a critical step in the propagation of the prion-like determinant [PSI+] of Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences of the United States of America, 97 (1). pp. 240-244. ISSN 0027-8424. (The full text of this publication is not available from this repository)

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Official URL
http://dx.doi.org/10.1073/pnas.97.1.240

Abstract

The cytoplasmic heritable determinant [PSI+] of the yeast Saccharomyces cerevisiae reflects the prion-like properties of the chromosome-encoded protein Sup35p. This protein is known to be an essential eukaryote polypeptide release factor, namely eRF3. In a [PSl(+)] background, the prion conformer of Sup35p forms large oligomers, which results in the intracellular depletion of functional release factor and hence inefficient translation termination. We have investigated the process by which the [PSI+] determinant can be efficiently eliminated from strains, by growth in the presence of the protein denaturant guanidine hydrochloride (GuHCl). Strains are "cured" of [PSI+] by millimolar concentrations of GuHCl, well below that normally required for protein denaturation. Here we provide evidence indicating that the elimination of the [PSI+] determinant is not derived from the direct dissolution of self-replicating [PSI+] seeds by GuHCl. Although GuHCl does elicit a moderate stress response, the elimination of [PSI+] is not enhanced by stress, and furthermore, exhibits an absolute requirement for continued cell division. We propose that GuHCl inhibits a critical event in the propagation of the prion conformer and demonstrate that the kinetics of curing by GuHCl fit a random segregation model whereby the heritable [PSI+] element is diluted from a culture. after the total inhibition of prion replication by GuHCl.

Item Type: Article
Uncontrolled keywords: curing; Sup35p; cytoplasmic determinant
Subjects: Q Science
Divisions: Faculties > Science Technology and Medical Studies > School of Biosciences
Depositing User: O.O. Odanye
Date Deposited: 19 May 2009 01:41
Last Modified: 04 May 2012 15:52
Resource URI: http://kar.kent.ac.uk/id/eprint/16060 (The current URI for this page, for reference purposes)
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