title: The structural impact of DNA mismatches.
abstract: 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.
authors.affiliation: Joint BSC-CRG-IRB Program on Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac, 10, Barcelona 08028, Spain Computational Biophysics, German Research School for Simulation Sciences (Joint venture of RWTH Aachen University and Forschungszentrum Jülich, Germany), D-52425 Jülich, Germany and Institute for Advanced Simulation IAS-5, Computational Biomedicine, Forschungszentrum Jülich, D-52425 Jülich, Germany Juelich Supercomputing Center (JSC), Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Giulia
authors.initials: G
authors.lastname: Rossetti
authors.affiliation: Joint BSC-CRG-IRB Program on Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac, 10, Barcelona 08028, Spain.
authors.forename: Pablo D
authors.initials: PD
authors.lastname: Dans
authors.affiliation: Joint BSC-CRG-IRB Program on Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac, 10, Barcelona 08028, Spain Instituto de Química Física Rocasolano, CSIC, C/Serrano 119, Madrid 28006, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Gomez-Pinto
authors.affiliation: Joint BSC-CRG-IRB Program on Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac, 10, Barcelona 08028, Spain.
authors.forename: Ivan
authors.initials: I
authors.lastname: Ivani
authors.affiliation: Instituto de Química Física Rocasolano, CSIC, C/Serrano 119, Madrid 28006, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Gonzalez
authors.affiliation: Joint BSC-CRG-IRB Program on Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac, 10, Barcelona 08028, Spain Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Avgda Diagonal 647, Barcelona 08028, Spain modesto.orozco@irbbarcelona.org.
authors.forename: Modesto
authors.initials: M
authors.lastname: Orozco
mesh_terms: D020137:Base Pair Mismatch; D004247:DNA / Q000737:chemistry*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation
chemical_list: D004247:DNA
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