title: Sequence-specific B-DNA flexibility modulates Z-DNA formation.
abstract: Conversion of right-handed B-DNA into left-handed Z-DNA is one of the largest structural transitions in biology that plays fundamental roles in gene expression and regulation. Z-DNA segments must form within genomes surrounded by a sea of B-DNA and require creation of energetically costly B/Z junctions. Here, we show using a combination of natural abundance NMR R(1ρ) carbon relaxation measurements and CD spectroscopy that sequence-specific B-DNA flexibility modulates the thermodynamic propensity to form Z-DNA and the location of B/Z junctions. We observe sequence-specific flexibility in B-DNA spanning fast (ps-ns) and slow (μs-ms) time scales localized at the site of B/Z junction formation. Further, our studies show that CG-repeats play an active role tuning this intrinsic B-DNA flexibility. Taken together, our results suggest that sequence-specific B-DNA flexibility may provide a mechanism for defining the length and location of Z-DNA in genomes.
authors.affiliation: Department of Chemistry and Biophysics, University of Michigan, Ann Arbor, Michigan 48109, United States.
authors.forename: Jameson R
authors.initials: JR
authors.lastname: Bothe
authors.forename: Ky
authors.initials: K
authors.lastname: Lowenhaupt
authors.forename: Hashim M
authors.initials: HM
authors.lastname: Al-Hashimi
mesh_terms: D001483:Base Sequence; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D043542:DNA, Z-Form / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data
chemical_list: D043542:DNA, Z-Form; D004247:DNA