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Title: Studies on bacterial gene transposition
Author: Wilkins, Gary Mark
ISNI:       0000 0001 3568 3188
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 1987
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(1) Two Escherichia coli K12 based transposition frequency assay systems have been designed and developed to allow the frequency of prokaryotic transposable element movements to be simply assayed. One of these systems involves the giant transposon bacteriophage Mu dl(ApRlac), that carries the P-galactosidase gene so that insertion adjacent to promotors can be quantified. The other system developed involves transposon 5 (Tn5), initially inserted in the host genome, that encodes kanamycin resistance which allows transposition to (and amplification in) plasmids to be quantified. (2) The most transposogenic compounds identified in the two transposition frequency assays are the alkyl-nitro-nitrosoguanidine alkylating agents. Most other alkylating agents exam­ined were either weakly transposogenic or non-transposogenic. (3) The alkyl-nitro-nitrosoguanidines appear to act by guanylate cyclase activation, via nitroxide radical release, and subsequent elevation of the cGMP concentration. The transposogen- icity of cGMP is confirmed by an apparant effect of permeable cGMP derivatives on Mu d\(ApRlac) and Tn5 transposition frequency. (4) A group of metals were examined for transposogenicity, and showed that transposogeni- city may be related to mutagenicity since mutagenic metals (Cd(II), Cr(VI) and Mn(II)) are tran­sposogenic and an anti-mutagenic metal (Co(II)) is anti-transposogenic. (5) The majority of transposogens identified in the two transposition frequency assays were mutagens, well documented in literature, and the putative non-transposogens were non- mutagenic. However, one group of compounds investigated were three non-mutagenic (Ames test negative) carcinogens. Diethylstilbesuol, DDT and o-toluidine each gave increases in Mu d\{ApRlac) transposition frequency which, although weak effects, might not have been expected from the other data, which suggested that mutagenicity and transposogenicity are inter-connected.
Supervisor: Not available Sponsor: Science and Engineering Research Council ; Imperial Chemical Industries Ltd ; University of Warwick
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QH426 Genetics