A common chemical mechanism used for DNA cleavage by copper(II) activated by thiols and ascorbate is distinct from that for copper(II): hydrogen peroxide cleavage

Summary By use of a [³²P] end-labelled 163 base pair linear fragment of duplex DNA isolated from tyrTDNA, the apparent sequence selectivity previously reported for DNA cleavage by Cu^II:thiol systems was shown to be identical to the sequence selectivity in scission shown by the Cu^II:ascorbate system. On this basis, a general mechanism of DNA cleavage is proposed for Cu^II with reducing agents including thiols as well as reducing sugars, including ascorbate and glucosamine. This mechanism involves hydroxyl radical generation and leads to both base damage and strand scission, and based on results with Cu^II:thiol cleavage the former occurs before the latter is detectable. Cleavage of DNA by Cu^II:hydrogen peroxide follows a different chemical mechanism, distinguishable by its different sequence preference.