Replication fidelity in the mircroevolution of mycobacteria

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.

Grantor dc:publisher.institution

Division of Medical Biochemistry

Year dc:date.issued

2015

Author dc:creator

• Ditse, Zanele

Advisors dc:contributor.advisor

• Warner, Digby F
• Mizrahi, Valerie

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/11427/15541

OAI identifier oai:identifier

oai:open.uct.ac.za:11427/15541