A precise interchromosomal reciprocal exchange between hot spots for cleavable complex formation by topoisomerase II in amsacrine-treated Chinese hamster ovary cells

Among the aprt mutations induced in confluence-arrested Chinese hamster ovary D422 cells by the topoisomerase II poison amsacrine, there was a reciprocal exchange between the aprt gene and an unrelated sequence, accompanied by a chromosomal translocation at the aprt locus. The breakpoints in both parental sequences were hot spots for amsacrine-stimulated DNA cleavage in vitro, and the novel junctions formed were precisely as expected for a mechanism involving reciprocal exchange of topoisomerase II subunits followed by resealing of the breaks and correction of mismatches in the cohesive ends. The results are consistent with a role for direct subunit exchange in the production of chromosomal translocations by topoisomerase poisons, although more complex models involving double-strand breakage and repair could produce reciprocal exchanges of similar specificity.