Impact of site-specific benzo[A]pyrene diol epoxide-DG lesions at or near single/doublestrand DNA junctions on DNA bending

Adducts derived from the binding of the (+)-7R,8S,9S,10R and (-)-7S,8R,9R,1 0S enantiomers of r7,t8-dihydrodiol-t9,10-epoxy-7,8,9,10-tetrahydrobenzo[a] pyrene (anti-BPDE) to 2'-deoxyguanosine residues in DNA are known to induce mutations due to error-prone DNA replication. Because the conformational p roperties of these lesions may be important in these phenomena, we have exa mined the effects Of the stereoisomeric (+)- and (-)-trans-anri-[BP]-N (2)- dG lesions positioned site-specifically at or near primer/template oligonuc leotide junctions on DNA bending using high resolution gel electrophoresis. Remarkable differences in electrophoretic mobilities mu are observed in th e two adducts derived from the tumorigenic (+)-anti-BPDE, and the non-tumor igenic (-)-anti-BPDE enantiomer. With the (+)-trans lesion positioned on th e template strand adjacent to the 3'-end of the primer strand, a remarkable decrease in mu is observed. This suggests the existence of a bend at the s ingle strand-double strand junction. Only modest decreases in mu are observ ed in the case of the (-)-trans lesion, or when the 3'-end is opposite to, or more distant from the lesion site. These observations are discussed in t erms of the known NMR solution structures of these lesions in the same sequ ence context, and the properties of primer/template DNA in polymerases.