title: A precise interchromosomal reciprocal exchange between hot spots for cleavable complex formation by topoisomerase II in amsacrine-treated Chinese hamster ovary cells.
abstract: 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.
authors.affiliation: Department of Pharmacology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Zhou
authors.forename: P
authors.initials: P
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Zou
authors.forename: C K
authors.initials: CK
authors.lastname: Jackson-Cook
authors.forename: L F
authors.initials: LF
authors.lastname: Povirk
mesh_terms: D000228:Adenine Phosphoribosyltransferase / Q000235:genetics*; D000677:Amsacrine / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D016466:CHO Cells / Q000187:drug effects; D002874:Chromosome Mapping; D006224:Cricetinae; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D015321:Gene Rearrangement / Q000235:genetics*; D008969:Molecular Sequence Data; D017384:Sequence Deletion; D014178:Translocation, Genetic
chemical_list: D000970:Antineoplastic Agents; D000677:Amsacrine; D000228:Adenine Phosphoribosyltransferase; D004250:DNA Topoisomerases, Type II