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Title: P53 and chromosome instability
Author: Strefford, Jon C.
Awarding Body: University of Wales Swansea
Current Institution: Swansea University
Date of Award: 2000
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This research project utilised methodologies from the fields of genetic toxicology and cytogenetic to accurately assess chromosome damage in p53-modified cell lines. Three primary diploid fibroblast cell lines were used; a control cell exhibited wild-type p53 characteristics, a mutant p53 cell line with a codon 143val-ala mutation, and a near null cell line containing transcripts for the E6 onco-fragments from the human papillomavirus type 16. These cell lines were characterised cytogenetically, and treated with genotoxic compounds so that the degree of chromosome damage could be assessed and correlated to p53 functional status. The mutant p53 plasmid induced significantly higher levels of spontaneous damage and premature centromeric division. After G1 and G2 chemical treatment, the E6 cell lines exhibited a significantly higher frequency of chromosome breakage, supporting the previous observations that p53 monitors these stages of the cell cycle. Chromosome painting and centromeric FISH for chromosome 1, 7 and 17 showed a shift towards abnormalities of chromosome 17 in the p53-modified cell lines. Post-treatment with a spindle poison, chromosome loss and non-disjunction were elevated in the p53 modified cell lines, implicating p53 as a monitoring protein in proper spindle formation. Treatment with Diazepam, showed ambiguous results, but suggested a limited role of p53 during centriole formation. This study demonstrated several p53-dependent monitoring capacities throughout cell cycle progression, several of which were novel observations. Premature centromeric division showed a clear correlation with changes in p53 functional status.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available