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Title: Regulation of telomere length in mammalian cells
Author: Rahman, Ruman
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2007
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Mammalian telomere length is regulated in a dynamic manner through multi-factorial elements. This project focuses on specific aspects of both extrinsic and intrinsic factors that govern telomere length. Expression of the human telomerase and reverse transcriptase (hTERT) gene in sheep fibroblasts reconstitutes telomerase activity and extends their lifespan. Although stabilization of telomere length is directly correlated to hTERT expression level, this was not reflected in telomerase activity. Data presented here shows that overexpression of non-catalytic domains decreased telomerase activity, compromised senescence bypass status and did not enhance telomere maintenance, which may result from competitive binding to sheep TR molecules and/or disruption of hTERT homodimeric structure. These results are consistent with the notion that telomere maintenance requires a functional telomerase complex which contains an inter-dependent hTERT homodimeric structure. The single-stranded 3’ G-rich overhang has been implicated as a key feature with a telomeric end-protection configuration. Data presented here show that the 3’ overhand is eroded during culture of sheep fibroblasts, indicating that the 3’ overhang length shortens prior to replicative senescence in cultured sheep fibroblasts. Furthermore, a correlation between hTERT expression level, karyotypic stability and 3’ overhang length is observed. This project also demonstrated that first application of the Quantitative-FISH (Q-FISH) and Telomere-Oligonucleotide Ligation Assay (T-OLA) techniques in the sheep model system.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available