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Site-specific cleavage of single-stranded DNAs at unique sites by a copper-dependent redox reaction

Abstract

Metal ions play a crucial role not only in the formation and maintenance of nucleic acid structure, but also in important biochemical conversions of polynucleotides. Some aqueous metal ions, acting as general acid/base (or electrophilic/nucleophilic) catalysts, can induce site-specific cleavage of RNA1–6. DNA is not cleaved efficiently by the non-redox metal-induced mechanism7. However, DNA degradation by radicals formed in the metal-catalysed auto-oxidation of ascorbate (or other reducing agents) is well known8–11. In the past, the observed cleavage reactions have not been very specific. Here, we report a non-enzymatic cleavage of single-stranded DNA occurring at unique sites due to redox reactions involving copper. This could be considered a 'self-cleavage' reaction, by analogy with the lead-induced non-redox RNA cleavage reaction3–5. This site-specific cleavage of DNA, stimulated by ascorbate and hydrogen peroxide, is most efficient under physiological conditions, so this phenomenon may have biological significance.

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Kazakov, S., Astashkina, T., Mamaev, S. et al. Site-specific cleavage of single-stranded DNAs at unique sites by a copper-dependent redox reaction. Nature 335, 186–188 (1988). https://doi.org/10.1038/335186a0

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