Abstract
HOMOPYRIMIDINE oligonucleotides bind to homopurine–homopyrimidine sequences of duplex DNA forming a local triple helix1–8. This binding can be demonstrated either directly by a footprinting technique3, gel assays4, or indirectly by inducing irreversible reactions in the target sequence, such as photocrosslinking1,5 or cleavage2,6–8. Binding occurs in the major groove with the homopyrimidine oligonucleotide orientated parallel to the homopurine strand. Thymine and protonated cytosine in the oligonucleotide form Hoogsteen-type hydrogen bonds with A·T and G·C Watson–Crick base pairs, respectively. Here we report that an 11-residue homopyrimidine oligonucleotide covalently attached to an ellipticine derivative by its 3' phosphate photo-induces cleavage of the two strands of a target homopurine–homopyrimidine sequence. To our knowledge, this is the first reported case of a sequence-specific artificial photoendonuclease. In addition we show that a strong binding site for a free ellipticine derivative is induced at the junction between the triplex and duplex structures on the 5' side of the bound oligonucleotide. On irradi-ation, cleavage is observed on both strands of DNA. This opens new possibilities for inducing irreversible reactions on DNA at specific sites by the synergistic action of a triple helix-forming oligonucleotide and an intercalating agent.
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Perrouault, L., Asseline, U., Rivalle, C. et al. Sequence-specific artificial photo-induced endonucleases based on triple helix-forming oligonucleotides. Nature 344, 358–360 (1990). https://doi.org/10.1038/344358a0
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DOI: https://doi.org/10.1038/344358a0
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