PMID: 8596537Feb 15, 1996Paper

Effects of DNA topoisomerase inhibitors on nonhomologous and homologous recombination in mammalian cells

Mutation Research
Y ArataniH Koyama

Abstract

To study the involvement of DNA topoisomerases in recombination in mammalian cells, we used gene transfer assays to examine the effects of DNA topoisomerase inhibitors on nonhomologous (illegitimate) and homologous recombination. The assays were performed by transfecting adenine phosphoribosyltransferase-deficient (APRT-) CHO cells with plasmids carrying the wild-type or mutant aprt genes and by treating the cells with the inhibitors, followed by subsequent cultivation to select for APRT-positive (APRT+) colonies. Treatments with DNA topoisomerase II inhibitors such as VP-16, VM-26, ICRF-193 resulted in a 3- to 5-fold stimulation of integration of both closed-circular and linearized plasmids carrying the wild-type aprt gene into the recipient genome through nonhomologous recombination. The same treatments also increased 6- to 9-fold and 3-fold the number of APRT+ recombinant colonies that were generated by cotransfecting two closed-circular plasmids with nonoverlapping defective aprt genes and their linearized equivalents, respectively. However, this cotransfection assay involved intrinsically nonhomologous recombination processes; normalization of the frequencies by dividing them with those of the above nonhomologous recombina...Continue Reading

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Citations

Apr 21, 2009·Nature Reviews. Cancer·John L Nitiss
Oct 11, 2001·Proceedings of the National Academy of Sciences of the United States of America·N AdachiH Koyama
Nov 2, 2015·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·P MosessoS Cinelli
Jun 15, 2001·The Journal of Biological Chemistry·S P Sim, L F Liu

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