Sequence-specific artificial photo-induced endonucleases based on triple helix-forming oligonucleotides.

Abstract:

:Homopyrimidine oligonucleotides bind to homopurine-homopyrimidine sequences of duplex DNA forming a local triple helix. This binding can be demonstrated either directly by a footprinting technique, gel assays, or indirectly by inducing irreversible reactions in the target sequence, such as photocrosslinking or cleavage. 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 irradiation, 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.

journal_name

Nature

journal_title

Nature

authors

Perrouault L,Asseline U,Rivalle C,Thuong NT,Bisagni E,Giovannangeli C,Le Doan T,Hélène C

doi

10.1038/344358a0

subject

Has Abstract

pub_date

1990-03-22 00:00:00

pages

358-60

issue

6264

eissn

0028-0836

issn

1476-4687

journal_volume

344

pub_type

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