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The Effect of the NADPH Oxidase YNO1 on Translational Fidelity

Dowling, James (2018) The Effect of the NADPH Oxidase YNO1 on Translational Fidelity. Master of Science by Research (MScRes) thesis, University of Kent,. (KAR id:73128)

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Abstract

The hypothesized relationship between translational fidelity and ageing is complex, dating back

half a century and so far represented by few known conclusions. Translational fidelity is known

to remain constant with ageing, but the mechanism through which this is possible is currently a

mystery. Recently, the yeast NADPH oxidase Yno1p was implicated in the regulation of

translational fidelity, and the relationship between Yno1p and translational fidelity was

investigated here in more detail. Through luciferase-based translational fidelity assays, here

was shown that YNO1 expression is negatively correlated with high frequency of stop-codon

read-through, and this pattern is mimicked by overnight ROS exposure, providing evidence that

ROS produced by Yno1p improves translational fidelity. Furthermore, YCK1, YCK2 and HEK2

was shown to be independently essential in mediating the fidelity improvement signal from

Yno1p to the translational machinery. Additionally, the mechanism by which hydrogen peroxide

exposure and Yno1p improves fidelity appears to be independent, but both can produce additive

improvements in fidelity. Using growth assays, overexpression of YNO1 and hydrogen peroxide

exposure were both shown to increase sensitivity to nourseothricin (NTC), a translational error-

inducing drug. YNO1 was found to be an important regulator of translational fidelity.

Item Type: Thesis (Master of Science by Research (MScRes))
Thesis advisor: Gourlay, Campbell
Thesis advisor: von der Haar, Tobias
Uncontrolled keywords: yeast cerevisiae yno1 yno1p aim14 translation translational accuracy fidelity luciferase ros ageing
Divisions: Divisions > Division of Natural Sciences > Biosciences
SWORD Depositor: System Moodle
Depositing User: System Moodle
Date Deposited: 22 Mar 2019 16:10 UTC
Last Modified: 20 May 2021 13:27 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/73128 (The current URI for this page, for reference purposes)
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