Cisplatin was found to be a potent recombinogen in comparison to the therapeutically inactive trans isomer of the drug. The hyper-recombinogenic property of cisplatin, activating various recombination pathways, may be of central importance for understanding the numerous cellular responses to the drug. To answer this question, the model organism Escherichia coli will be used because more genes affecting recombination are known than in any other. A recombination assay system employing duplicated lac operons will used to assay drug-induced recombination in strains mutated in various recombination genes. In addition, mutations in genes affecting DNA replication and repair will also be tested as these are probably required for repair and restarting DNA replication.
Recombination is probably important for cellular resistance to drugs other than cisplatin.
Various strains defective in different recombination pathways will be used to monitor drug-sensitivity. Hyper-recombination induced by cisplatin. Drug concentration, on small circular disks, increases in a counter-clockwise manner with the control at the top. Escherichia coli mutator genes. Trends in Microbiology .