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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...
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| Format: | Thesis |
| Language: | English |
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Division of Medical Biochemistry
2015
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| _version_ | 1867613247966806016 |
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| access_status_str | Open Access |
| author | Ditse, Zanele |
| author2 | Warner, Digby F |
| author_browse | Ditse, Zanele Warner, Digby F |
| author_facet | Warner, Digby F Ditse, Zanele |
| author_sort | Ditse, Zanele |
| collection | Thesis |
| description | 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. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/15541 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:33:07.122Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2015 |
| publishDateRange | 2015 |
| publishDateSort | 2015 |
| publisher | Division of Medical Biochemistry |
| publisherStr | Division of Medical Biochemistry |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/15541 Replication fidelity in the mircroevolution of mycobacteria Ditse, Zanele Warner, Digby F Mizrahi, Valerie Medical Microbiology 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. 2015-12-03T14:10:54Z 2015-12-03T14:10:54Z 2015 Doctoral Thesis Doctoral PhD http://hdl.handle.net/11427/15541 eng application/pdf Division of Medical Biochemistry Faculty of Health Sciences University of Cape Town |
| spellingShingle | Medical Microbiology Ditse, Zanele Replication fidelity in the mircroevolution of mycobacteria |
| thesis_degree_str | Doctoral |
| title | Replication fidelity in the mircroevolution of mycobacteria |
| title_full | Replication fidelity in the mircroevolution of mycobacteria |
| title_fullStr | Replication fidelity in the mircroevolution of mycobacteria |
| title_full_unstemmed | Replication fidelity in the mircroevolution of mycobacteria |
| title_short | Replication fidelity in the mircroevolution of mycobacteria |
| title_sort | replication fidelity in the mircroevolution of mycobacteria |
| topic | Medical Microbiology |
| url | http://hdl.handle.net/11427/15541 |
| work_keys_str_mv | AT ditsezanele replicationfidelityinthemircroevolutionofmycobacteria |