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Sequence specific cleavage of DNA by the antitumor antibiotics neocarzinostatin and bleomycin.
Open accessAbstract
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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Citations
Cited by
ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks
Jazayeri, A., Falck, J., Lukas, C., Bartek, J., Smith, G. C. M., Lukas, J., & Jackson, S. P. (2006) · Nature Cell Biology · doi:10.1038/ncb1337 · Cited by 1,064
MUTAGENESIS BY APURINIC/APYRIMIDINIC SITES
Loeb, L. A., & Preston, B. D. (1986) · Annual Review of Genetics · doi:10.1146/annurev.ge.20.120186.001221 · Cited by 901
Teicher, B. A. (1994) · Cancer and Metastasis Reviews · doi:10.1007/bf00689633 · Cited by 563
DNA double-strand breaks caused by replication arrest
Michel, B. (1997) · The EMBO Journal · doi:10.1093/emboj/16.2.430 · Cited by 426
Bleomycin‐induced strand‐scission of DNA. Mechanism of deoxyribose cleavage
Giloni, L., Takeshita, M., Johnson, F., Iden, C., & Grollman, A. P. (1981) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)68888-5 · Cited by 412
Metadata
- Authors
- D'Andrea, A. D., & Haseltine, W. A.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1978-08
- Volume
- 75
- Issue
- 8
- Pages
- 3608-3612
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2033800372
- Cited by
- 302
- References
- 0
- FWCI
- 10.57
- Type
- journal article
- Language
- en
- Open access
- green
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- D'Andrea, A. D., & Haseltine, W. A. (1978). Sequence specific cleavage of DNA by the antitumor antibiotics neocarzinostatin and bleomycin. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.75.8.3608
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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