title: The binding of the Co(II) complex of dimeric chromomycin A3 to GC sites with flanking G:G mismatches.
abstract: Some neurological diseases are correlated with expansion of (CXG)n trinucleotide repeats, which contain many contiguous GpC flanked by mismatched X/X base pair. This study focused on the binding of the Co(II) complex of dimeric chromomycin A3(Chro), Co(II)(Chro)2, to DNA with CXG trinucleotide repeats. The present study showed that GC sites with flanking G:G mismatches provide an excellent binding site for Co(II)(Chro)2 as shown by surface plasmon resonance and fluorescence analysis, compared to GC sites with flanking A:A, T:T, or C:C mismatches. In addition, we measured the ability of Co(II)(Chro)2 to act on the hairpin DNA of (CGG)16. We observed that Co(II)(Chro)2 could stabilize and trap the cruciform conformation of (CGG)16. Furthermore, two Co(II)(Chro)2 molecules may bind at the two GpC sites separated by at least one GC site in the hairpin structure of (CGG)16. In a synthetic self-priming DNA model, 5'-(CGG)16(CCG)6-3', Co(II)(Chro)2 can interfere with the expansion process of CGG triplet repeats, as shown by a gel electrophoretic expansion assay. Here, we first report the acting of Co(II)(Chro)2, the groove-binding drug, to trinucleotide repeats. Our results provide the possible biological consequence of Co(II)(Chro)2 bound to CGG triplet repeat sequences.
authors: Institute of Biotechnology, National Chung Hsing University, Taichung, 402 Taiwan.
authors: Yu-Wen
authors: YW
authors: Chen
authors: Ming-Hon
authors: MH
authors: Hou
mesh_terms: D020137:Base Pair Mismatch; D020029:Base Pairing; D001665:Binding Sites; D014128:Chromomycin A3 / Q000737:chemistry*; D056831:Coordination Complexes / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000138:chemical synthesis / Q000737:chemistry*; D019281:Dimerization; D024202:Electrophoretic Mobility Shift Assay; D007700:Kinetics; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D020349:Surface Plasmon Resonance; D018911:Trinucleotide Repeats
chemical_list: D056831:Coordination Complexes; D003300:Copper; D004247:DNA; D014128:Chromomycin A3