Rad51 overexpression and resistance to genotoxic agents. A study in the fission yeast Schizosaccharomyces pombe.
Year: 2014
Type: article
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 rad51 gene 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.
Source: The Medical-Surgical Journal
Institution: Grigore T. Popa University of Medicine and Pharmacy
Language: English
Topic: DNA Repair Mechanisms
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W2410775767