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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1978 Aug;75(8):3608–3612. doi: 10.1073/pnas.75.8.3608

Sequence specific cleavage of DNA by the antitumor antibiotics neocarzinostatin and bleomycin.

A D D'Andrea, W A Haseltine
PMCID: PMC392834  PMID: 80799

Abstract

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.

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Selected References

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