PMID: 8604323Feb 15, 1996Paper

Structure and dynamics of the DNA hairpins formed by tandemly repeated CTG triplets associated with myotonic dystrophy

Nucleic Acids Research
S V MariappanG Gupta

Abstract

Anomalous expansion of the DNA triplet (CTG)n causes myotonic dystrophy. Structural studies have been carried out on (CTG)n repeats in an attempt to better understand the molecular mechanism of repeat expansion. NMR and gel electrophoretic studies demonstrate the presence of hairpin structures for (CTG)5 and (CTG)6 in solution. The monomeric hairpin structure remains invariant over a wide range of salt concentrations (10-200 mM NaCl), DNA concentrations (micromolar to millimolar in DNA strand) and pH (6.0-7.5). The (CTG)n hairpin contains three bases in the loop when n is odd and four bases when n is even. For both odd and even n the stacking and pairing in the stem remain the same, i.e, two hydrogen bond T.T pairs stack with the neighboring G.C pairs. All the nucleotides in (CTG)5 and (CTG)6 adopt C2'-endo, anti conformations. Full-relaxation matrix analysis has been performed to derive the NOE distance constraints from NOESY experiments at seven different mixing times (25, 50, 75, 100, 125, 200 and 500 ms). NOESY-derived distance constraints were subsequently used in restrained molecular dynamics simulations to obtain a family of structures consistent with the NMR data. The theoretical order parameters are computed for H5-H6(...Continue Reading

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Citations

Jul 17, 1998·Current Opinion in Structural Biology·C E Pearson, R R Sinden
May 8, 2010·Chemical Communications : Chem Comm·Arivazhagan RajendranNaoki Sugimoto
Mar 26, 1998·Journal of Biomolecular Structure & Dynamics·S V MariappanG Gupta
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