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dc.contributor.advisorSchweizer, Professor Michael
dc.contributor.authorUgbogu, Eziuche Amadike
dc.date.accessioned2016-10-14T16:39:33Z
dc.date.available2016-10-14T16:39:33Z
dc.date.issued2014-10
dc.identifier.urihttp://hdl.handle.net/10399/2948
dc.description.abstractThe products of the five-membered PRS gene family in S. cerevisiae exist as three entities, Prs1/Prs3, Prs2/Prs5 and Prs4/Prs5, each capable of supporting cell viability. The signal generated from an integrated GFP-Prs1 construct is dependent on the presence of Prs3. Prs1 not only interacts with Prs3 but also with Slt2, the MAPK of the Cell Wall Integrity (CWI) pathway as shown by co-immunoprecipitation and confirming previous Y2H studies that the central region of Prs1, NHR1-1, is essential for the interaction with the CWI pathway. Point mutations in PRS1 corresponding to missense mutations associated with human neuropathies or in the divalent cation- and/or PRPP-binding sites interfere with CWI signalling resulting in temperature and/or caffeine sensitivity. The synthetic lethality of a strain lacking PRS1 and PRS5 can only be rescued by versions of Prs1 containing NHR1-1, implying that impaired CWI contributes to this loss of viability. Prs5 is unusual in that it contains two NHRs, one, NHR5-2, contains three phosphorylation sites. Mutation of these amino acid residues impinges on the expression of the transcription factor, Rlm1, an endpoint of the CWI pathway and reduces the temperature-dependent transcription of FKS2, the gene encoding the stress-induced catalytic subunit of 1,3-β-glucan synthase essential for maintaining CWI. This finding emphasizes the functionality of the three phosphorylation sites located in NHR5-2 of Prs5. The data presented support the hypothesis that the PRS gene family has, as a result of gene duplication and acquisition of NHRs, evolved to link primary metabolism with CWI.en_US
dc.language.isoenen_US
dc.publisherHeriot-Watt Universityen_US
dc.publisherLife Sciencesen_US
dc.rightsAll items in ROS are protected by the Creative Commons copyright license (http://creativecommons.org/licenses/by-nc-nd/2.5/scotland/), with some rights reserved.
dc.titleThe PRS gene family links primary metabolism and cell signalling in Saccharomyces cerevisiaeen_US
dc.typeThesisen_US


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