NMR-based structural studies of damaged DNAs

The structures of duplex DNAs containing damaged sites can be determined by the combined use of NMR and restrained molecular dynamics. The NMR of DNAs containing abasic sites can be challenging since there are two equilibrating forms of the abasic site present. The damaged sites also tend to have fewer NOE connectivities than conventional DNA. Nevertheless, sufficient experimental NMR data can be obtained on these samples and the procedures for refining the structures by restrained molecular dynamics are sufficiently robust for structures to be determined. Two case studies are presented. In one case it is shown that the presence of an abasic site gives rise to large-scale structural disruption when within a sequence that can give rise to DNA curvature. In the other case, a thymine glycol leads to structural changes primarily at, and adjacent to, the damaged site. © 1996 by John Wiley & Sons, Ltd.