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Echinomycin, a bis-intercalating agent, induces C-->T mutations via cytosine deamination.

Publication ,  Journal Article
Moyer, R; Briley, D; Johnsen, A; Stewart, U; Shaw, BR
Published in: Mutation research
August 1993

Echinomycin, a bis-intercalating, antitumor drug, has been studied for its ability to induce the deamination of cytosine to uracil (C-->U) in double-stranded DNA. We have employed a sensitive lacZ alpha-complementation reversion assay to detect G.C-->A.T mutations at a number of sites in M13mp2 DNA to determine the extent to which distortions of DNA structure induced by echinomycin may affect C-->U rates. When double-stranded M13mp2 DNA with a 12-base target containing a CpG site was incubated at 37 degrees C, the reversion frequency of the echinomycin-treated DNA increased linearly over time, with a rate constant 3-fold greater than DNA incubated without echinomycin. Of the 11 ways that blue pseudo-revertants can occur in the target, 96% of the observed revertants arose from C-->T and tandem CC-->TT transitions, with 78% attributable to single-base C-->T changes at three sites. Transfection into ung+ cells decreased the reversion frequencies by 85% to near background levels, indicating that the increase in C-->T mutations was due to deamination of C to U. The cytosine deamination rate constants for the entire target at pH 6.0 and 37 degrees C were 1.2 x 10(-11) sec-1 for untreated DNA and 3.5 x 10(-11) sec-1 for echinomycin-treated DNA. The increase in C-->T mutation rates occurred at cytosines both proximal and distal to a CpG echinomycin-binding site. We hypothesize that this increase in deamination rate is due to a more open or single-stranded DNA structure caused by the echinomycin: DNA interaction.

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Published In

Mutation research

DOI

EISSN

1873-135X

ISSN

0027-5107

Publication Date

August 1993

Volume

288

Issue

2

Start / End Page

291 / 300

Related Subject Headings

  • Transfection
  • Temperature
  • Oncology & Carcinogenesis
  • Mutation
  • Mutagenesis, Site-Directed
  • Molecular Sequence Data
  • Intercalating Agents
  • Echinomycin
  • Deamination
  • Cytosine
 

Citation

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Moyer, R., Briley, D., Johnsen, A., Stewart, U., & Shaw, B. R. (1993). Echinomycin, a bis-intercalating agent, induces C-->T mutations via cytosine deamination. Mutation Research, 288(2), 291–300. https://doi.org/10.1016/0027-5107(93)90097-y
Moyer, R., D. Briley, A. Johnsen, U. Stewart, and B. R. Shaw. “Echinomycin, a bis-intercalating agent, induces C-->T mutations via cytosine deamination.Mutation Research 288, no. 2 (August 1993): 291–300. https://doi.org/10.1016/0027-5107(93)90097-y.
Moyer R, Briley D, Johnsen A, Stewart U, Shaw BR. Echinomycin, a bis-intercalating agent, induces C-->T mutations via cytosine deamination. Mutation research. 1993 Aug;288(2):291–300.
Moyer, R., et al. “Echinomycin, a bis-intercalating agent, induces C-->T mutations via cytosine deamination.Mutation Research, vol. 288, no. 2, Aug. 1993, pp. 291–300. Epmc, doi:10.1016/0027-5107(93)90097-y.
Moyer R, Briley D, Johnsen A, Stewart U, Shaw BR. Echinomycin, a bis-intercalating agent, induces C-->T mutations via cytosine deamination. Mutation research. 1993 Aug;288(2):291–300.

Published In

Mutation research

DOI

EISSN

1873-135X

ISSN

0027-5107

Publication Date

August 1993

Volume

288

Issue

2

Start / End Page

291 / 300

Related Subject Headings

  • Transfection
  • Temperature
  • Oncology & Carcinogenesis
  • Mutation
  • Mutagenesis, Site-Directed
  • Molecular Sequence Data
  • Intercalating Agents
  • Echinomycin
  • Deamination
  • Cytosine