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Title: Telomeric silencing, nucleotide excision repair and chromatin organisation in Saccharomyces cerevisiae
Author: Ona, Agurtzane Irizar
ISNI:       0000 0004 2749 0951
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2009
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In this thesis, the influence of subtelomeric silencing on chromatin structure and Nucleotide excision repair (NER) efficiency in Saccharomyces cerevisiae is addressed. To assess the chromatin organisation, NER efficiency and acetylation levels yeast strains containing the URA3 marker gene at two subtelomeres with distinct levels of silencing were used. All the analyses were undertaken at the coding region of the URA3 sequence. Overall, the results presented in this thesis showed that at subtelomeres with high levels of silencing, the DNA is less accessible to the NER machinery therefore, the repair is slower. This is probably due to the variations in chromatin organisation since the chromatin structure is more compact at highly silenced subtelomeres. When telomeric silencing is abrogated by the deletion of the SIR2 gene, the NER efficiency and the chromatin organisation became similar at both subtelomeres, enforcing the idea that the differences in NER and chromatin organisation are due to variations in silencing levels. Furthermore, there was a considerable difference at the highly silenced subtelomere between the SIR2+ and sir2A strains. However, the differences at the non-highly silenced telomeres between SIR2+ and sir2A were not so dramatic. This work also concentrated on the inhibitory role of Sir2p on the acetylation response after UV irradiation. The results showed an incremental increase in acetylation levels after UV treatment when the SIR2 gene was deleted at the highly repressive end. However, the acetylation levels remained the same after and before the UV treatment when SIR2 was not deleted. In contrast, there were not significant differences in acetylation levels between the SIR2+ and the sir2A strains after UV irradiation at the non-repressive end. These findings imply that silencing influence NER efficiency and DNA accessibility. Furthermore, SIR2 suppresses any UV induced response in acetylation at highly silenced subtelomeres.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available