Journal of Inorganic Biochemistry 2013-04-01

The binding of the Co(II) complex of dimeric chromomycin A3 to GC sites with flanking G:G mismatches.

Yu-Wen Chen, Ming-Hon Hou

文献索引：J. Inorg. Biochem. 121 , 28-36, (2013)

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摘要

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.Copyright © 2012 Elsevier Inc. All rights reserved.