The Role of DNA Repair in Resistance to Topoisomerase Inhibitor and Nucleoside Analogues

Abstract

Mutations in DNA repair genes often leads to cancer. Cancer cells created this way can be sensitive to the DNA damaging drugs, which are still primary cancer treatment. In response to topoisomerase inhibitors such as Camptothecin, Mre11 (a DNA repair nuclease), has been shown to remove topoisomerases from DNA. The same activity of this nuclease DNA repair has also been shown to be responsible for the nucleotide removal from DNA ends. Recent work indicates that mutation in other DNA repair genes could sensitise the treatment of nucleoside analogues and topoisomerase inhibitors. Synthetic lethality (e.g. PARP inhibitors) is one way to exploit mutations of DNA repair genes in cancer cells. The aim of this study is to identify interaction of synthetic lethality between mre11-D65N (nuclease dead mutant) and other DNA repair mutants as well as to identify a combination of double mutant that may increase sensitivity to numerous DNA damaging drugs.