This thesis aimed to elucidate the structure-function relationships determining the differential fidelities of the dnaE1- and dnaE2-encoded mycobacterial PolIIIα subunits under conditions of genotoxic stress. To this end, the role in DnaE1 intrinsic fidelity of highly conserved PHP domain residues was explored by site-directed replacement of targeted amino acids, resulting in a panel of Mycobacterium smegmatis mutants carrying selected dnaE1 alleles. A complementary approach investigated the contribution of the mycobacterial proofreading DnaQ subunit homolog to the maintenance of DnaE1-dependent replicative fidelity by generating a targeted dnaQ knockout mutant. The third component of this study focused on the inferred role of a highly-conserved N-terminal extension and C-terminal pentapeptide motif in the function of the alternative, error-prone DNA PolIIIα subunit, DnaE2.
Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:uct/oai:localhost:11427/15541 |
Date | January 2015 |
Creators | Ditse, Zanele |
Contributors | Warner, Digby F, Mizrahi, Valerie |
Publisher | University of Cape Town, Faculty of Health Sciences, Division of Medical Biochemistry |
Source Sets | South African National ETD Portal |
Language | English |
Detected Language | English |
Type | Doctoral Thesis, Doctoral, PhD |
Format | application/pdf |
Page generated in 0.0019 seconds