Prediction of structural perturbations caused by uracil, dihydrouracil and cytosine hydrate in a DNA decamer duplex from the adenovirus E2A promoter by molecular modeling

Ionizing radiation and oxidizing agents produce a variety of base damage products in the genomic DNA of all living organisms. The biological relevance of the structural changes that uracil, dihydrouracil and cytosine hydrate may induce stems from the fact that all of these lesions are derived from cytosine in vivo and are potentially premutagenic. To gain further insight into the structural basis for DNA damage recognition by redoxyendonucleases, the authors have carried out computer-assisted molecular modeling of single-site pyrimidine damages in a 10-base-pair DNA duplex that forms the activating transcription factor (ATF) binding site within the adenovirus E2A promoter. Molecular modeling predictions are valuable in that they give an estimate of the stability, conformations and possibly the biological lifetime of the altered residue in the damaged DNA