Effect of base sequence context on the conformational heterogeneity of aristolactam-I adducted DNA: structural and energetic insights into sequence-dependent repair and mutagenicity.

ABSTRACT: Aristolochic acids (AAs) are nephrotoxic and potentially carcinogenic plant mutagens that form bulky DNA adducts at the exocyclic amino groups of the purines. The present work utilizes classical molecular dynamics simulations and free energy calculations to investigate the role of lesion site sequence context in dictating the conformational outcomes of DNA containing ALI-N⁶-dA, the most persistent and mutagenic adduct arising from the AAs. Our calculations reveal that the anti base-displaced intercalated conformer is the lowest energy conformer of damaged DNA in all sequence contexts considered (CXC, CXG, GXC and GXG). However, the experimentally-observed greater mutagenicity of the adduct in the CXG sequence context does not correlate with the relative thermodynamic stab

SUBMITTER: Kathuria P 

PROVIDER: S-EPMC6061885 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature