title: Interlocked mismatch-aligned arrowhead DNA motifs.
abstract: BACKGROUND
  Triplet repeat sequences are of considerable biological importance as the expansion of such tandem arrays can lead to the onset of a range of human diseases. Such sequences can self-pair via mismatch alignments to form higher order structures that have the potential to cause replication blocks, followed by strand slippage and sequence expansion. The all-purine d(GGA)n triplet repeat sequence is of particular interest because purines can align via G.G, A.A and G.A mismatch formation.
  
  
  RESULTS
  We have solved the structure of the uniformly 13C,15N-labeled d(G1-G2-A3-G4-G5-A6-T7) sequence in 10 mM Na+ solution. This sequence adopts a novel twofold-symmetric duplex fold where interlocked V-shaped arrowhead motifs are aligned solely via interstrand G1.G4, G2.G5 and A3.A6 mismatch formation. The tip of the arrowhead motif is centered about the p-A3-p step, and symmetry-related local parallel-stranded duplex domains are formed by the G1-G2-A3 and G4-G5-A6 segments of partner strands.
  
  
  CONCLUSIONS
  The purine-rich (GGA)n triplet repeat sequence is dispersed throughout the eukaryotic genome. Several features of the arrowhead duplex motif for the (GGA)2 triplet repeat provide a unique scaffold for molecular recognition. These include the large localized bend in the sugar-phosphate backbones, the segmental parallel-stranded alignment of strands and the exposure of the Watson-Crick edges of several mismatched bases.
authors.affiliation: Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: A
authors.initials: A
authors.lastname: Kettani
authors.forename: S
authors.initials: S
authors.lastname: Bouaziz
authors.forename: E
authors.initials: E
authors.lastname: Skripkin
authors.forename: A
authors.initials: A
authors.lastname: Majumdar
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: R A
authors.initials: RA
authors.lastname: Jones
authors.forename: D J
authors.initials: DJ
authors.lastname: Patel
mesh_terms: D020137:Base Pair Mismatch; D001483:Base Sequence; D004247:DNA / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011522:Protons; D018911:Trinucleotide Repeats
chemical_list: D011522:Protons; D004247:DNA