The structural impact of DNA mismatches.
|The structural impact of DNA mismatches.
|Year of Publication
|Rossetti, Giulia, Dans Pablo D., Gómez-Pinto Irene, Ivani Ivan, González Carlos, and Orozco Modesto
|Nucleic Acids Res
|2015 Apr 30
|Base Pair Mismatch, DNA, Models, Molecular, Nucleic Acid Conformation
The structure and dynamics of all the transversion and transition mismatches in three different DNA environments have been characterized by molecular dynamics simulations and NMR spectroscopy. We found that the presence of mismatches produced significant local structural alterations, especially in the case of purine transversions. Mismatched pairs often show promiscuous hydrogen bonding patterns, which interchange among each other in the nanosecond time scale. This therefore defines flexible base pairs, where breathing is frequent, and where distortions in helical parameters are strong, resulting in significant alterations in groove dimension. Even if the DNA structure is plastic enough to absorb the structural impact of the mismatch, local structural changes can be propagated far from the mismatch site, following the expected through-backbone and a previously unknown through-space mechanism. The structural changes related to the presence of mismatches help to understand the different susceptibility of mismatches to the action of repairing proteins.