Antibiotic drugs aminoglycosides cleave DNA at abasic sites: shedding new light on their toxicity?

Abasic sites are probably the most common lesions in DNA resulting from the hydrolytic cleavage of glycosidic bonds that can occur spontaneously and through DNA alkylation by anticancer agents, by radiotherapy, and during the repair processes of damaged nucleic bases. If not repaired, the abasic site can be mutagenic or lethal. Thus, compounds able to specifically bind and react at abasic sites have attracted much attention for therapeutic and diagnostic purposes. Here, we report on the efficient cleavage activity of characteristic antibiotic drugs of the major aminoglycosides (AG) family at abasic sites introduced either by depurination in a plasmidic DNA or site specifically in a synthetic oligonucleotide. Among the antibiotic AG drugs selected for this study, neomycin B is the most efficient (a 0.1 μM concentration induces 50% cleavage of an abasic site containing DNA). This cleavage activity could be related to aminoglycoside toxicity but also find medicinal applications through potentiation of cancer...