NMR Structural Study of the 3'-T？G Mismatched DNA Decamer Duplea Containing the T-T (6-4) Adduct

Abstract

The pyrimidine(6-4) pyrimidone photoproduct [(6-4) adduct] is one of the major photoproducts induced by UV irradiation of DNA and occurs at TpT sites. The (6-4) adduct is highly mutagenic and specific during translesion replication. The marked preference for insertion of A opposite the 5-T and G opposite the 3-T of the (6-4) adducts leads to a predominantly 3-TC transition with 85% replicating error rate. In order to obtain insight into the origin of 3’-TC transition induced by the (6-4) adduct, we have performed one - and two-dimensional NMR experiment. The 3-T of the (6-4) lesion forms the stable hydrogen bonding to the imino proton of an opposed G, which stabilizes the overall helix and diminishes the highly distorted conformation caused by the (6-4) lesion in the (6-4)/AA duplex. We proposed that the greater insertion of a G over an A opposite the 3-T of the (6-4) lesion These results may account for the greater preference for the insertion of a G over an A opposite the 3-T of the (6-4) lesion. Thus this insertion leads to the highly specific 3-TC mutation at the (6-4) lesion site.