Destabilization of DNA duplexes by oxidative damage at guanine: implications for lesion recognition and repair.

ABSTRACT: We have used molecular dynamics simulations to study the structure and dynamics of a range of DNA duplexes containing the 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapydG) lesion that can result from oxidative damage at guanine. Compared to the corresponding undamaged DNA duplexes, FapydG-containing duplexes show little gross structural changes-the damaged base remains stacked in to the DNA double helix and retains hydrogen bonds to its cytosine partner. However, the experimentally observed reduction in DNA stability that accompanies lesion formation can be explained by a careful energetic analysis of the simulation data. Irrespective of the nature of the base pairs on either side of the lesion site, conversion of a guanine to a FapydG base results in increased dynamical flexibility in

SUBMITTER: Jiranusornkul S 

PROVIDER: S-EPMC2586096 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature