NMR-BASED STRUCTURAL STUDIES OF DAMAGED DNAS

The structures of duplex DNAs containing damaged sites can be determin ed by the combined use of NMR and restrained molecular dynamics, The N MR of DNAs containing abasic Bites 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, Neve rtheless, sufficient experimental NMR data can be obtained on these sa mples and the procedures for refining the structures by restrained mol ecular dynamics are sufficiently robust for structures to be determine d. Two case studies are presented, In one case it is shown that the pr esence of an abasic site gives rise to large-scale structural disrupti on 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.