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

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dc.contributor.authorBrackin, Robyn
dc.date.accessioned2006-11-17T09:04:27Z
dc.date.available2006-11-17T09:04:27Z
dc.date.issued2006-11-17T09:04:27Z
dc.descriptionFaculty of Science School of Pathology 9903547r robyn.brakin@gmail.comen
dc.description.abstractMycobacterium 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.extent2539581 bytes
dc.format.extent14615 bytes
dc.format.mimetypeapplication/pdf
dc.format.mimetypeapplication/pdf
dc.identifier.urihttp://hdl.handle.net/10539/1842
dc.language.isoenen
dc.subjectbacteriaen
dc.subjectY-familyen
dc.subjectpathogenen
dc.subjecthumanen
dc.subjecttuberculosisen
dc.titleExpression and function of the mutator DNA polymerasencoding umuC-like genes in mycobacteriaen
dc.typeThesisen
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