Rad51 overexpression and resistance to genotoxic agents. A study in the fission yeast Schizosaccharomyces pombe.
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.
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.
We used the nmt1 promoter inserted upstream of rad51 gene to induce its overexpression and studied the phenotype of the transformed strain, especially its sensitivity to camptothecin and hydroxyurea.
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.
Stanescu RS, Bordeianu G, Stoica B, Ungureanu D, Rusu M, Petrescu-Danila E