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Science 3 September 1993:
Vol. 261. no. 5126, pp. 1319 - 1321
DOI: 10.1126/science.8362243
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Articles

Science, Vol 261, Issue 5126, 1319-1321
Copyright © 1993 by American Association for the Advancement of Science

articles

DNA conformation-induced activation of an enediyne for site-specific cleavage

LS Kappen and IH Goldberg

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.

Neocarzinostatin chromophore (NCS chrom) was found to induce site-specific 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 generated an ultraviolet light-absorbing and fluorescent species of post-activated 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 generate this drug product. Thus, DNA is an active participant in its own destruction, and NCS chrom may be useful as a probe for bulged structures in nucleic acids.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Solution NMR Structure Investigation for Releasing Mechanism of Neocarzinostatin Chromophore from the Holoprotein.
H. Takashima, T. Yoshida, T. Ishino, K. Hasuda, T. Ohkubo, and Y. Kobayashi (2005)
J. Biol. Chem. 280, 11340-11346
   Abstract »    Full Text »    PDF »
Rapid PCR amplification of minimal enediyne polyketide synthase cassettes leads to a predictive familial classification model.
W. Liu, J. Ahlert, Q. Gao, E. Wendt-Pienkowski, B. Shen, and J. S. Thorson (2003)
PNAS 100, 11959-11963
   Abstract »    Full Text »    PDF »
Gene transcription analysis of Saccharomyces cerevisiae exposed to neocarzinostatin protein- chromophore complex reveals evidence of DNA damage, a potential mechanism of resistance, and consequences of prolonged exposure.
S. E. Schaus, D. Cavalieri, and A. G. Myers (2001)
PNAS 98, 11075-11080
   Abstract »    Full Text »    PDF »


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