Faculty of Science
School of Pathology
9903547r
robyn.brakin@gmail.com / Mycobacterium tuberculosis is an important human pathogen, claiming more lives per annum than any other single infectious organism. The host environment of M. tuberculosis contains DNA-damaging agents that pose a constant threat to the M. tuberculosis genome, and as a result, the ability to repair damaged DNA is likely to play an important role in bacterial survival. Y-family polymerases perform translesional synthesis and replicate DNA in an error-prone manner. By characterising the Y-family polymerases in mycobacteria, a better understanding the organism’s adaptive mutagenesis may be established.
Through gene expression studies, it was found that UV irradiation of Mycobacterium smegmatis resulted in the up-regulation of dinP3, which was determined to be a Y-family polymerase by sequence analysis. DinP3 expression was found to be under control of the SOS response and is the first example of a Y-family polymerase in mycobacteria forming part of the SOS regulon. However, loss of DinP3 did not change the ability of M. smegmatis to tolerate UV irradiation. Mutagenesis studies revealed a complex interaction between the different Y-family polymerases in M. smegmatis. It was shown that spontaneous mutagenesis was increased in the absence of DinP3, whereas UV-targeted mutagenesis was increased in the absence of DinP, another Y-family polymerase.
In conclusion, these results reflect the differences in control and in the mutational profiles of the Y-family polymerases in M. smegmatis. Moreover, these polymerases exhibit distinctive features from other bacterial Y-family polymerases, highlighting the different way in which bacteria have adapted to deal with lesions in their genetic material.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/1842 |
| Date | 17 November 2006 |
| Creators | Brackin, Robyn |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 2539581 bytes, 14615 bytes, application/pdf, application/pdf, application/pdf, application/pdf |
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