Rapid Identification of Chemoresistance Mechanisms Using Yeast DNA Mismatch Repair Mutants.

ABSTRACT: Resistance to cancer therapy is a major obstacle in the long-term treatment of cancer. A greater understanding of drug resistance mechanisms will ultimately lead to the development of effective therapeutic strategies to prevent resistance from occurring. Here, we exploit the mutator phenotype of mismatch repair defective yeast cells combined with whole genome sequencing to identify drug resistance mutations in key pathways involved in the development of chemoresistance. The utility of this approach was demonstrated via the identification of the known CAN1 and TOP1 resistance targets for two compounds, canavanine and camptothecin, respectively. We have also experimentally validated the plasma membrane transporter HNM1 as the primary drug resistance target of mechlorethamine. Furthermore, th

SUBMITTER: Ojini I 

PROVIDER: S-EPMC4555229 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature