RAD51 OVEREXPRESSION AND RESISTANCE TO GENOTOXIC AGENTS. A STUDY IN THE FISSION YEAST SCHIZOSACCHAROMYCES POMBE
Abstract
Background: Many cancer cell lines have been found to overexpress the recombinase Rad51. The overexpression is associated with increased invasive potential and resistance to DNA-damaging therapeutic agents. This has been attributed to an increased capacity of cells overexpressing Rad51 to repair DNA lesions or to a genetic stabilization of the genome. Aim: As the explanations are somewhat controversial, we attempted to reproduce overexpression in the unicellular eukaryote Schizosaccharomyces pombe to have a simpler tool to study the problem of Rad51 overexpression and its induced resistance to DNA-damaging agents. Methods: We used the nmt1 promoter inserted upstream of rad51gene to induce its overexpression and studied the phenotype of the transformed strain, especially its sensitivity to camptothecin and hydroxyurea. Results: We found that overexpression induced sensitivity to the two drugs even when it was associated with the deletion of a recombination mediator rad22/rad52 gene. However, when overexpression was associated with the deletion of the helicase-encoding fbh1 gene, the sensitivity to camptothecin was diminished.
References
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