Two methods of treatment where this is especially important to consider are topoisomerase inhibitors and nucleoside analogues. In both of these cases, DNA repair systems involve the use of the Mre11/Rad50/NBS1 complex. This project aims to examine how DNA repair mechanisms of Schizosaccharomyces pombe contribute to resistance to treatment with nucleoside analogues. This information should help to provide further insight into the way in which human cells are able to develop resistance to this form of treatment, and perhaps provide some indication of a method to prevent this. C.
LIST OF ABBREVIATIONS adh constitutive promoter promoter of alcohol dehydrogenase °C degrees centigrade (degree celsius) dH2O distilled water DNA: deoxyribonucleic acid DSB double strand break dsDNA double-stranded DNA F forward KanMX kanamycin (G418) resistance marker L litre Mg milligram Ml millilitre mM millimolar NAT nourseothricin resistance marker PCR polymerase chain reaction R reverse Ura auxotroph marker 3′ Three prime end of DNA 5′ Five prime end of DNA Table of Contents B.
Abstract 5 Chapter One: 9 1.1.
Introduction 9 1.2. DNA repair and cancer 11 1.3. DNA replication 12 1.4. DNA repair 14 1.5. MRN Complex 17 1.6. Topoisomerase inhibitors 18 1.7. Nucleoside analogues 20 1.8. Involvement of DNA repair 24 1.9.