title: Structural deviations at CpG provide a plausible explanation for the high frequency of mutation at this site. Phosphorus nuclear magnetic resonance and circular dichroism studies.
abstract: CpG sites in DNA are hotspots for mutations leading to human genetic disorders. However, the structural basis for these events were still unclear and necessitated a deeper evaluation. Our experiments with phosphorus-31 nuclear magnetic resonance, ultraviolet-melting and circular dichroism on two related CpG-containing octanucleotide duplexes show that CpG is a malleable step whose conformation and thermal stability are strongly dependent on the nature of its flanking steps. We conclude that the CpG step may exert a deleterious structural influence on the helix very much like the mismatch containing steps. This peculiar property of CpG should constitute a molecular basis for its recognition by various ligands as well as for mutations affecting CpG and hence an explanation for its rarity in vertebrate genomes.
authors: Pharmacologie Moléculaire (CNRS URA 147, INSERM U 140), Institut Gustave Roussy Villejuif, France.
authors: S
authors: S
authors: el Antri
authors: O
authors: O
authors: Mauffret
authors: M
authors: M
authors: Monnot
authors: E
authors: E
authors: Lescot
authors: O
authors: O
authors: Convert
authors: S
authors: S
authors: Fermandjian
mesh_terms: D001483:Base Sequence; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000235:genetics*; D015226:Dinucleoside Phosphates / Q000737:chemistry*; D004355:Drug Stability; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D009154:Mutation; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D004247:DNA; D015226:Dinucleoside Phosphates; D009838:Oligodeoxyribonucleotides; C015772:CpG dinucleotide