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Title: Factors affecting de novo formation of a yeast prion
Author: Stojanovski, Klement
Awarding Body: University of Kent
Current Institution: University of Kent
Date of Award: 2012
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Prions are aggregates of misfolded proteins that have acquired an amyloid-like structure and ability to propagate through recruitment of new proteins. [PSI+], a prion form of eukaryotic release factor Sup35 (eRF1) is widely used as a model for research on prion formation and propagation and in this study [PSI+] is used to explore an effect of three previously identified proteins on de novo prion formation. One mechanism proposed to affect prion formation is direct interaction of Sup35p with its binding partners and search for proteins that interact with Sup35p identified Ppq 1 p, a putative Ser/Thr protein phosphatase (M.F. Tuite and T. von der Haar). Another approach was to identify proteins that function to protect translational apparatus from environmental and . endogenous oxidative damage. and this approach identified two ribosome associated peroxiredoxins, Tsa1 p and Tsa2p (T. Sideri and C.M. Grant). The data presented here shows that the deletion of PPQ1 gene greatly increases the rate of de novo formation of [PSI+] but the mechanism by which loss of Ppq1 p affects [PSI+] formation is not known. Analysis of the distribution of fluorescently-tagged Ppq 1 P showed that the protein co-localises with mitochondria. A further line of evidence linking Ppq 1 P to mitochondria was an observed reduction in respiratory capacity of a ppq1 Δ strain. That exposure to environmental sources of oxidative stress promotes [PSI+] prion formation was previously reported (Tyedmers et al., 2008). Results presented here show that an endogenous source of oxidative stress, brought about by deleting the ribosomally- associated peroxiredoxins (Prx) encoded by genes TSA 1/2 (Trotter et al., 2008; Sideri et al., 2010), also increases the rate of de novo [PSI+]formation. This result provides a direct link between oxidative stress and the eukaryotic release factor Sup35p.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available