Position-specific trapping of topoisomerase I-DNA cleavage complexes by intercalated benzo[a]- pyrene diol epoxide adducts at the 6-amino group of adenine.

ABSTRACT: DNA topoisomerase I (top1) is the target of potent anticancer agents, including camptothecins and DNA intercalators, which reversibly stabilize (trap) top1 catalytic intermediates (cleavage complexes). The aim of the present study was to define the structural relationship between the site(s) of covalently bound intercalating agents, whose solution conformations in DNA are known, and the site(s) of top1 cleavage. Two diastereomeric pairs of oligonucleotide 22-mers, derived from a sequence used to determine the crystal structure of top1-DNA complexes, were synthesized. One pair contained either a trans-opened 10R- or 10S-benzo[a]pyrene 7, 8-diol 9,10-epoxide adduct at the N(6)-amino group of a central 2'-deoxyadenosine residue in the scissile strand, and the other pair contained the same two

SUBMITTER: Pommier Y 

PROVIDER: S-EPMC27093 | biostudies-literature | 2000 Sep

REPOSITORIES: biostudies-literature