Anthraquinone photonucleases: A surprising role for chloride in the sequence-neutral cleavage of DNA and the footprinting of minor groove-bound ligands

Irradiation of water-soluble anthraquinone (AQ) reagents in the presence of chloride ions results in the spontaneous, sequence-neutral cleavage of DNA, Mechanistic studies indicate that cleavage is initiated by chlorine atoms, produced by charge transfer interaction between chloride anion and AQ triplet states, High-resolution gel electrophoresis suggests that cleavage arises from abstraction of a hydrogen atom from C-4' of deoxyribose units. The targeting of this hydrogen, which is located in the minor groove of duplex DNA, can be effectively blocked by netropsin and, to a lesser degree, berenil, leading to photofootprinting of these minor groove-binding drugs.