Neocarzinostatin chromophore (NCS chrom) was found to induce site-spec
ific cleavage at the 3' side of a bulge in single-stranded DNA in the
absence of thiol. This reaction involved the oxidative formation of a
DNA fragment with a nucleoside 5'-aldehyde at its 5' terminus and gene
rated an ultraviolet light-absorbing and fluorescent species of post-a
ctivated drug containing tritium abstracted from the carbon at the 5'
position of the target nucleotide. The DNAs containing point mutations
that disrupt the bulge were not cleavage substrates and did not gener
ate this drug product. Thus, DNA is an active participant in its own d
estruction, and NCS chrom may be useful as a probe for bulged structur
es in nucleic acids.