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. 1990 Mar 1;266(2):379–384. doi: 10.1042/bj2660379

Effects of DNA-binding drugs on T4 DNA ligase.

A Montecucco 1, G Pedrali-Noy 1, S Spadari 1, M Lestingi 1, G Ciarrocchi 1
PMCID: PMC1131142  PMID: 2156493

Abstract

A number of DNA intercalating and externally binding drugs have been found to inhibit nick sealing, cohesive and blunt end ligation, AMP-dependent DNA topoisomerization and EDTA-induced DNA nicking mediated by bacteriophage T4 DNA ligase. The inhibition seems to arise from drug-substrate interaction so that formation of active DNA-Mg2(+)-AMP-enzyme complex is impaired while assembled and active complexes are not disturbed by drug binding to the substrate.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barker D. G., Johnson A. L., Johnston L. H. An improved assay for DNA ligase reveals temperature-sensitive activity in cdc9 mutants of Saccharomyces cerevisiae. Mol Gen Genet. 1985;200(3):458–462. doi: 10.1007/BF00425731. [DOI] [PubMed] [Google Scholar]
  2. Depew D. E., Wang J. C. Conformational fluctuations of DNA helix. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4275–4279. doi: 10.1073/pnas.72.11.4275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Fareed G. C., Richardson C. C. Enzymatic breakage and joining of deoxyribonucleic acid. II. The structural gene for polynucleotide ligase in bacteriophage T4. Proc Natl Acad Sci U S A. 1967 Aug;58(2):665–672. doi: 10.1073/pnas.58.2.665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Howell S. H., Stern H. The appearance of DNA breakage and repair activities in the synchronous meiotic cycle of Lilium. J Mol Biol. 1971 Feb 14;55(3):357–378. doi: 10.1016/0022-2836(71)90323-8. [DOI] [PubMed] [Google Scholar]
  5. Kalisch B. W., van de Sande J. H. The effect of antibiotics on the T4 polynucleotide ligase catalyzed template dependent polymerization of oligodeoxythymidylates. Nucleic Acids Res. 1979;6(5):1881–1894. doi: 10.1093/nar/6.5.1881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kapuściński J., Szer W. Interactions of 4', 6-diamidine-2-phenylindole with synthetic polynucleotides. Nucleic Acids Res. 1979 Aug 10;6(11):3519–3534. doi: 10.1093/nar/6.11.3519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Lehman I. R. DNA ligase: structure, mechanism, and function. Science. 1974 Nov 29;186(4166):790–797. doi: 10.1126/science.186.4166.790. [DOI] [PubMed] [Google Scholar]
  8. Manzini G., Xodo L., Barcellona M. L., Quadrifoglio F. Interaction of DAPI with double-stranded ribonucleic acids. Nucleic Acids Res. 1985 Dec 20;13(24):8955–8967. doi: 10.1093/nar/13.24.8955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Modrich P., Lehman I. R. Enzymatic characterization of a mutant of Escherichia coli with an altered DNA ligase. Proc Natl Acad Sci U S A. 1971 May;68(5):1002–1005. doi: 10.1073/pnas.68.5.1002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Modrich P., Lehman I. R., Wang J. C. Enzymatic joining of polynucleotides. XI. Reversal of Escherichia coli deoxyribonucleic acid ligase reaction. J Biol Chem. 1972 Oct 10;247(19):6370–6372. [PubMed] [Google Scholar]
  11. Montecucco A., Ciarrocchi G. AMP-dependent DNA relaxation catalyzed by DNA ligase occurs by a nicking-closing mechanism. Nucleic Acids Res. 1988 Aug 11;16(15):7369–7381. doi: 10.1093/nar/16.15.7369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Montecucco A., Pedrali-Noy G., Spadari S., Ciarrocchi G. Multiple roles of DNA ligase at the replication fork. Biochim Biophys Acta. 1988 Dec 20;951(2-3):330–334. doi: 10.1016/0167-4781(88)90103-0. [DOI] [PubMed] [Google Scholar]
  13. Montecucco A., Pedrali-Noy G., Spadari S., Zanolin E., Ciarrocchi G. DNA unwinding and inhibition of T4 DNA ligase by anthracyclines. Nucleic Acids Res. 1988 May 11;16(9):3907–3918. doi: 10.1093/nar/16.9.3907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Pedrini A. M., Ciarrocchi G. Inhibition of Micrococcus luteus DNA topoisomerase I by UV photoproducts. Proc Natl Acad Sci U S A. 1983 Apr;80(7):1787–1791. doi: 10.1073/pnas.80.7.1787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Rabin B. A., Chase J. W. DNA ligase from Drosophila melanogaster embryos. Substrate specificity and mechanism of action. J Biol Chem. 1987 Oct 15;262(29):14105–14111. [PubMed] [Google Scholar]
  16. Spadari S., Ciarrocchi G., Falaschi A. Purification and properties of a polynucleotide ligase from human cell cultures. Eur J Biochem. 1971 Sep 13;22(1):75–78. doi: 10.1111/j.1432-1033.1971.tb01516.x. [DOI] [PubMed] [Google Scholar]
  17. Söderhäll S., Lindahl T. DNA ligases of eukaryotes. FEBS Lett. 1976 Aug 1;67(1):1–8. doi: 10.1016/0014-5793(76)80858-7. [DOI] [PubMed] [Google Scholar]
  18. Weiss B., Live T. R., Richardson C. C. Enzymatic breakage and joining of deoxyribonucleic acid. V. End group labeling and analysis of deoxyribonucleic acid containing single straned breaks. J Biol Chem. 1968 Sep 10;243(17):4530–4542. [PubMed] [Google Scholar]

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