title: Transient Hoogsteen base pairs in canonical duplex DNA.
abstract: Sequence-directed variations in the canonical DNA double helix structure that retain Watson-Crick base-pairing have important roles in DNA recognition, topology and nucleosome positioning. By using nuclear magnetic resonance relaxation dispersion spectroscopy in concert with steered molecular dynamics simulations, we have observed transient sequence-specific excursions away from Watson-Crick base-pairing at CA and TA steps inside canonical duplex DNA towards low-populated and short-lived A•T and G•C Hoogsteen base pairs. The observation of Hoogsteen base pairs in DNA duplexes specifically bound to transcription factors and in damaged DNA sites implies that the DNA double helix intrinsically codes for excited state Hoogsteen base pairs as a means of expanding its structural complexity beyond that which can be achieved based on Watson-Crick base-pairing. The methods presented here provide a new route for characterizing transient low-populated nucleic acid structures, which we predict will be abundant in the genome and constitute a second transient layer of the genetic code.
authors.affiliation: Department of Chemistry and Biophysics, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109, USA.
authors.forename: Evgenia N
authors.initials: EN
authors.lastname: Nikolova
authors.forename: Eunae
authors.initials: E
authors.lastname: Kim
authors.forename: Abigail A
authors.initials: AA
authors.lastname: Wise
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: O'Brien
authors.forename: Ioan
authors.initials: I
authors.lastname: Andricioaei
authors.forename: Hashim M
authors.initials: HM
authors.lastname: Al-Hashimi
mesh_terms: D020029:Base Pairing; D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D005815:Genetic Code; D006860:Hydrogen Bonding; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D011789:Quantum Theory; D013816:Thermodynamics
chemical_list: D004247:DNA