Thesis (Ph. D.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

Thesis (M.S. in genetics and cell biology)--Washington State University, August 2008. / Includes bibliographical references (p. 39-43).

Konstanz, Univ., Diss., 2007.

Techn. Hochsch., Diss., 2005--Aachen.

published_or_final_version / abstract / Physiology / Doctoral / Doctor of Philosophy

ABSTRACT Rifampicin is a major chemotherapeutic agent used against mycobacterial and nocardial infections. High level resistance is primarily due to mutational alterations in the rpoB gene encoding the β subunit of RNA polymerase. When challenged, these bacteria may inactivate rifampicin by one of four mechanisms: decomposition, ADP-ribosylation, glucosylation and phosphorylation. ADPribosylation occurs in many mycobacterial pathogens but nothing is known about the properties of the enzyme responsible. Consequently mutational analysis may be used to explore structure-function relationships in this protein. Three mutants with changes in the open reading frame were selected and studied. The altered arr gene in pMG1 was obtained by in vivo selection whilst in pMG2 and pMG4 by in vitro mutagenesis. The mutated arr gene in pMG1 and pMG2 conferred resistance to 50 μg/ml of rifampicin while in pMG4 to 200 μg/ml. This suggested that alterations near the N-terminus resulted in lowered activity because of closer proximity to the active site. This is the first successful report of induced arr gene expression. This over-expression of the Arr ADP-ribosyltransferase and its mutants assisted in their later purification by metal affinity chromatography.

Thesis (M.S.)--Rutgers University, 2009. / "Graduate Program in Microbiology and Molecular Genetics." Includes bibliographical references (p. 49-53).

DNA double strand breaks (DSBs) are primarily repaired in eukaryotic cells by two different mechanisms – non-homologous end joining (NHEJ) or homologous recombination (HR). In mammalian somatic cells the balance between the two highly favours NHEJ. Gene targeting is a technique that exploits HR repair to alter a defined gene locus. While it holds potential to be implemented as a treatment option for several diseases, the outlook for using it in a clinical setting has been obstructed by a low gene targeting efficiency. This has been coupled to the low frequency of HR in mammalian cells. With the intention of shifting the repair balance, antibodies against DSB repair proteins will be introduced into mammalian cells. It is predicted that by targeting key repair proteins with antibodies, a compensatory increase in the frequency of HR can be fostered, ultimately resulting in improved gene targeting. / xv, 168 leaves : ill. ; 29 cm

Konstanz, Univ., Diss., 2008.

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