Journal
JOURNAL OF INORGANIC BIOCHEMISTRY
Volume 121, Issue -, Pages 28-36Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2012.12.007
Keywords
Groove-binding drugs; Dimeric chromomycin A3; Cobalt; CGG triplet repeats; DNA expansion
Funding
- NSC grant [100-2113-M-005-004-MY3]
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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. (c) 2012 Elsevier Inc. All rights reserved.
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