Expression and function of the mutator DNA polymerasencoding umuC-like genes in mycobacteria

Show simple item record Brackin, Robyn 2006-11-17T09:04:27Z 2006-11-17T09:04:27Z 2006-11-17T09:04:27Z
dc.description Faculty of Science School of Pathology 9903547r en
dc.description.abstract 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. en
dc.format.extent 2539581 bytes
dc.format.extent 14615 bytes
dc.format.mimetype application/pdf
dc.format.mimetype application/pdf
dc.language.iso en en
dc.subject bacteria en
dc.subject Y-family en
dc.subject pathogen en
dc.subject human en
dc.subject tuberculosis en
dc.title Expression and function of the mutator DNA polymerasencoding umuC-like genes in mycobacteria en
dc.type Thesis en

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