Please use this identifier to cite or link to this item:
Full metadata record
DC FieldValueLanguage
dc.contributor.authorChan, Tsun Ho-
dc.descriptionPh. D. Thesisen_US
dc.description.abstractThe fission yeast, Schizosaccharomyces pombe is host to the Tf2 family of long terminal repeat (LTR) retrotransposons. Uncontrolled propagation of these elements is a potential threat to genomic integrity and therefore their expression and mobilization is subjected to strict control. To analyse the host factors and environmental stimuli that influence the propagation of Tf2 elements, an assay was employed that allows the mobilization frequency of a marked endogenous element (Tf2-12natAI) to be monitored. Using this assay it was determined that a high copy number of Tf1, a related Ty3/gypsy LTR retrotransposon, can stimulate Tf2 mobilization via a post-transcriptional mechanism that is dependent upon Tf1-encoded proteins. Indeed, the data suggest that Tf2 can hijack the propagation mechanisms of a Tf1 for its own use. During these studies it was discovered that the composition of the growth medium has a major impact upon Tf2 activity. Cell culture in minimal (EMM) medium, instead of rich (YE5S) medium, resulted in increased Tf2 expression and mobilization. The increased level of Tf2 activity resulted from some specific components of EMM medium, namely ammonium (NH4 + ) and phthalate ions. The finding that the growth medium influences Tf2 activity also prompted analysis of TORC signalling cascades which are master regulators of cellular responses to environment. Both the expression and mobilization of Tf2 elements was activated in response to exposure to rapamycin, a drug that forms a complex with the FKBP12 protein (Fkh1) and inhibits the activity of the TORC1 complex. This suggested that Tf2 activity is under the TORC1 control but surprisingly, the inhibition of TORC1 using a tor2 temperature sensitive allele or a direct chemical inhibitor (Torin1) did not activate the expression of Tf2 elements. Therefore, rapamycin influences the expression of Tf2 elements via a TORC1-independent pathway. This pathway was found to be dependent upon the FKBP12 protein Fkh1, the forkhead transcription factor Fhl1, a putative co-activator protein Crf1 and the Pka signalling pathwayen_US
dc.publisherNewcastle Universityen_US
dc.titleHost factors and environmental stimuli that regulate Schizosaccharomyces pombe LTR retrotransposonsen_US
Appears in Collections:Institute for Cell and Molecular Biosciences

Files in This Item:
File Description SizeFormat 
Chan 099220594 ethesis.pdfThesis4.88 MBAdobe PDFView/Open
dspacelicence.pdfLicence43.82 kBAdobe PDFView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.