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.
Zhou
R H
RH
Department of Pharmacology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA.
Wang
P
P
Zou
Y
Y
Jackson-Cook
C K
CK
Povirk
L F
LF
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
D000970:Antineoplastic Agents; D000677:Amsacrine; D000228:Adenine Phosphoribosyltransferase; D004250:DNA Topoisomerases, Type II