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Assessing the role of Hsp70 in prion propagation in Saccharomyces cerevisiae

Cusack, Sarah (2010) Assessing the role of Hsp70 in prion propagation in Saccharomyces cerevisiae. PhD thesis, National University of Ireland Maynooth.

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Abstract

The term Prion (Proteinaceous infectious) was first described by Stanley Prusiner in 1982. Prions are infectious proteins and are responsible for many neurodegenerative diseases, collectively termed as transmissible spongioform encephalopathies, including; BSE, vBSE, scrapie and CJD. Prions are also present in fungi. There have been a number of prion proteins discovered in the yeast Saccharomyces cerevisiae. Probably the most studied of these is the [PSI+], which is the prion form of the protein Sup35, which is required for the release of nascent polypeptide chains from the ribosome during translation termination. Studies indicate that the de novo formation and propagation of yeast prions require the function of protein chaperones and co-chaperones. The heat shock proteins (HSP) such as Hsp40, Hsp70 and Hsp104, are essential for prion propagation in yeast. Hsp70 is a highly conserved protein composed of an N-terminal ATPase domain, a peptide-binding domain (PBD) and a C-terminal domain. In this study we describe a genetic screen that identifies an array of mutants within different domains of the major cytosolic Hsp70 chaperones of yeast, Ssa1-4 which impair the propagation of [PSI+]. A majority of isolated mutants are located within the ATPase domain and have no significant affect on Hsp70 function. The PBD mutant Ssa1F475S, which impairs [PSI+] propagation also appears to make Ssa1 non-functional and may implicate Ssa1 in an array of cellular functions. We also highlight differences between the Hsp70 cytosolic Ssa family members with respect to prion propagation and Hsp70 function.

Item Type: Thesis (PhD)
Keywords: role of Hsp70; prion propagation; Saccharomyces cerevisiae;
Subjects: Science & Engineering > Biology
Item ID: 2567
Depositing User: IR eTheses
Date Deposited: 15 Jun 2011 13:52
URI:

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