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Title: Sensitivity to UV-damage in SV40-transformed Indian muntjac cells
Author: Howard, S. J.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 1998
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SVM87, is an SV40-transformed Indian muntjac cell line which has previously been shown, in comparison with a spontaneously transformed but non-isogenic cell line DM, to be unusually sensitive to UV-irradiation. UV-sensitivity cannot be explained by a difference in DNA repair capacity. In this dissertation work we have found that SV40-transofrmation is the cause of the SVM87 phenotype. Over seven independent SV40-transformed Indian muntjac cell lines have been examined and all shown to be sensitive to UV-damage, to the same extent as SVM87. Flow cytometry studies show that the sensitivity results from an inability of these cells to effectively replicate UV-damaged DNA. The cells exhibit slow S-phase progression, severe genomic instability and cell death following UV-irradiation. Examination of DNA replication intermediates, following UV-irradiation, show that single stranded DNA regions, containing UV-photoproducts, persist within the nascent fraction for extended periods of time in UV-sensitive, but not normal cell lines. In an attempt to identify the basis for this SV40 T-constructs was generated and examined. The results indicate that the critical region of the T-antigen for establishing the UV-sensitive phenotype resides within the N-terminus 147 amino acids for T-antigen. This region includes p300, polymerase α-primase and pRb binding domains.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available