title: Conformations of nicked and gapped DNA structures by NMR and molecular dynamic simulations in water.
abstract: We have analyzed and compared the molecular structures and dynamics of DNA duplexes containing a nick or a gap of one nucleotide where the base in front of the gap is a guanine. The continuous strand has the sequence 5'(CAGAGTCXCTGGCTC) where the residue X is absent for the nick, 14-mer, and where it is a G residue for the gap. Duplexes were formed with the two corresponding 7-mers. Neither of these is phosphorylated adjacent at the nick site, but it is a good model for a single strand break. For the nick structure, the quantitative NMR data show that the global conformation is very close to canonical B-form DNA, but it displays enhanced local flexibility. For the gap structure, we observe only one species in which the extra G is well stacked into the helix. The two half-helices around this residue also show a B-form conformation. As with the nick duplex, the adjacent G imino protons show enhanced exchange with solvent. The gap does not close completely. Using distance constraints, MD calculations show that the nick conformation is very close to a duplex with no lesion but is indeed more flexible in the central part. The gapped structure shows two families of conformations. One is close to B-DNA, the other is significantly kinked at the gap which reduces the size of the cavity. We observe a spine of hydration within the cavities, similar, but of different geometry in the two cases.
authors.affiliation: CEA, Service de Biochimie et de Génétique Moléculaire, Département de Biologie Cellulaire et Moléculaire, Gif-sur-Yvette, France.
authors.forename: C
authors.initials: C
authors.lastname: Roll
authors.forename: C
authors.initials: C
authors.lastname: Ketterlé
authors.forename: V
authors.initials: V
authors.lastname: Faibis
authors.forename: G V
authors.initials: GV
authors.lastname: Fazakerley
authors.forename: Y
authors.initials: Y
authors.lastname: Boulard
mesh_terms: D001482:Base Composition; D004247:DNA / Q000737:chemistry*; D004249:DNA Damage; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D009692:Nucleic Acid Heteroduplexes; D011522:Protons; D013696:Temperature; D013816:Thermodynamics; D014867:Water
chemical_list: D009692:Nucleic Acid Heteroduplexes; D011522:Protons; D014867:Water; D004247:DNA