Sequence specific cleavage of DNA by the antitumor antibiotics neocarzinostatin and bleomycin.
We have investigated the sites of DNA damage by the antitumor antibiotics neocarzinostatin and bleomycin by using a 5'-end-labeled DNA fragment of defined sequence as a substrate. At the high drug concentrations used here, neocarzinostatin creates single-strand breaks in DNA at positions of adenine and thymine in the presence of 2-mercaptoethanol, and bleomycin cleaves DNA at GC and GT sequences and to a lesser extent at TA sequences with its degradative activity enhanced by 2-mercaptoethanol. In the presence of ferrous ions, bleomycin cleaves DNA at TT, AT, and TA, as well as at GC and GT sequences. Both antibiotics make double-strand breaks in DNA at specific sites and it is likely that these result from two independent single-strand breaks at nearby sites on opposite strands of the DNA.
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001483:Base Sequence; D001665:Binding Sites; D001761:Bleomycin / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000378:metabolism; D007501:Iron / Q000494:pharmacology; D008623:Mercaptoethanol; D013379:Substrate Specificity; D009353:Zinostatin / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D004269:DNA, Bacterial; D001761:Bleomycin; D008623:Mercaptoethanol; D009353:Zinostatin; D007501:Iron