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Inhibition of DNA replication by a d(CAG) repeat binding ligand
Masaki Hagihara1, Kazuhiko Nakatani
1The Institute of Scientific and Industrial Research, Osaka University, Mihogaoka 8-1, Ibaraki, Osaka 567-0047, Japan.
Abstract:
Trinucleotide repeat expansions in genomic DNA are the molecular basis of a number of genetic diseases. The (CAG)n, (CTG)n, and (CGG)n repeats share the common sequence CXG, and inherently produce a hairpin structure involving X-X mismatch base pairs flanked by two G-C base pairs. The chance of a strand slippage leading to the repeat expansion is considered to increase with increasing stability of the hairpin form. Here we show our synthetic ligand naphthyridine-azaquinolone (NA) stabilized a hairpin form of the (CAG)n repeat and inhibited the polymerase-mediated DNA synthesis.
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