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Studies of Sup35p : a yeast prion protein

Eaglestone, Simon Spencer (1999) Studies of Sup35p : a yeast prion protein. Doctor of Philosophy (PhD) thesis, University of Kent. (doi:10.22024/UniKent/01.02.94320) (KAR id:94320)


[P S f] is a protein-based heritable phenotype of the yeast Saccharomyces cerevisiae that 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 /P S f] strain, the prion conformer of Sup35p exists predominantly as large oligomers, which results in the intracellular depletion of functional release factor (i.e. eRF3) and hence inefficient translation termination. Intriguingly, the prion conformer of Sup35p can be eliminated from [PSI+] strains by growth in the presence of the protein denaturant guanidine hydrochloride (GuHCl). Strains are ‘cured’ of [P S f] by millimolar concentrations of GuFICl, well below that normally required for protein denaturation. It was shown that the kinetics of GuHCl-induced curing fit a segregational model, whereby the heritable [P S f ] determinant is diluted from a culture following the total inhibition of prion replication. A hypothesis for the mechanism of curing is proposed namely that the guanidinium cation inhibits an arginine-modifying enzyme, whose action is required for the post-translational modification of Sup35p and ultimately [P S f] maintenance. The [P S f] determinant does not elicit a disease state in yeast, rather it was shown to confer a selective phenotypic advantage namely enhanced stress tolerance. Moreover, it was demonstrated that the efficiency of translation termination is regulated by environmental stress through a prion-mediated mechanism. This study has addressed the relationship between Sup35p, [PSP] and stress proteins of S.cerevisiae and revealed that prion proteins are not simply pathogenic misshapen proteins and that they may serve as a novel means to regulate many cellular processes in fungi.

Item Type: Thesis (Doctor of Philosophy (PhD))
DOI/Identification number: 10.22024/UniKent/01.02.94320
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Uncontrolled keywords: Biochemistry
Subjects: Q Science > QH Natural history > QH426 Genetics
Divisions: Divisions > Division of Natural Sciences > Biosciences
SWORD Depositor: SWORD Copy
Depositing User: SWORD Copy
Date Deposited: 18 May 2023 10:49 UTC
Last Modified: 18 May 2023 10:50 UTC
Resource URI: (The current URI for this page, for reference purposes)

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