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. 1983 Jan;153(1):379–383. doi: 10.1128/jb.153.1.379-383.1983

Distribution and specificity of mutations induced by neocarzinostatin in the lacI gene of Escherichia coli.

P L Foster, E Eisenstadt
PMCID: PMC217383  PMID: 6217195

Abstract

Although neocarzinostatin (NCS) attacks DNA almost exclusively at adenine and thymine residues in vitro, exposure of Escherichia coli to this antitumor drug resulted in a high frequency of mutations at guanine:cytosine base pairs in the lacI gene. Thus, NCS-induced base substitution mutations do not appear to result from the major DNA lesions that have been biochemically characterized. The overall distribution of nonsense mutations produced by NCS was distinctly nonrandom, consisting in part of a few "hotspots" and a large number of "coldspots." The existence of these coldspots implies that untargeted mutagenesis does not make a significant contribution to the mutations induced by this SOS-dependent mutagen.

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Selected References

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  1. Albers-Schönberg G., Dewey R. S., Hensens O. D., Liesch J. M., Napier M. A., Goldberg I. H. Neocarzinostatin: chemical characterization and partial structure of the non-protein chromophore. Biochem Biophys Res Commun. 1980 Aug 14;95(3):1351–1356. doi: 10.1016/0006-291x(80)91622-8. [DOI] [PubMed] [Google Scholar]
  2. Ames B. N., Lee F. D., Durston W. E. An improved bacterial test system for the detection and classification of mutagens and carcinogens. Proc Natl Acad Sci U S A. 1973 Mar;70(3):782–786. doi: 10.1073/pnas.70.3.782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Beerman T. A., Goldberg I. H. The relationship between DNA strand-scission and DNA synthesis inhibition in HeLa cells treated with neocarzinostatin. Biochim Biophys Acta. 1977 Mar 18;475(2):281–293. doi: 10.1016/0005-2787(77)90019-3. [DOI] [PubMed] [Google Scholar]
  4. Coulondre C., Miller J. H. Genetic studies of the lac repressor. III. Additional correlation of mutational sites with specific amino acid residues. J Mol Biol. 1977 Dec 15;117(3):525–567. doi: 10.1016/0022-2836(77)90056-0. [DOI] [PubMed] [Google Scholar]
  5. Coulondre C., Miller J. H. Genetic studies of the lac repressor. IV. Mutagenic specificity in the lacI gene of Escherichia coli. J Mol Biol. 1977 Dec 15;117(3):577–606. doi: 10.1016/0022-2836(77)90059-6. [DOI] [PubMed] [Google Scholar]
  6. D'Andrea A. D., Haseltine W. A. Sequence specific cleavage of DNA by the antitumor antibiotics neocarzinostatin and bleomycin. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3608–3612. doi: 10.1073/pnas.75.8.3608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Eisenstadt E., Warren A. J., Porter J., Atkins D., Miller J. H. Carcinogenic epoxides of benzo[a]pyrene and cyclopenta[cd]pyrene induce base substitutions via specific transversions. Proc Natl Acad Sci U S A. 1982 Mar;79(6):1945–1949. doi: 10.1073/pnas.79.6.1945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Eisenstadt E., Wolf M., Goldberg I. H. Mutagenesis by neocarzinostatin in Escherichia coli and Salmonella typhimurium: requirement for umuC+ or plasmid pKM101. J Bacteriol. 1980 Nov;144(2):656–660. doi: 10.1128/jb.144.2.656-660.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Foster P. L., Eisenstadt E., Cairns J. Random components in mutagenesis. Nature. 1982 Sep 23;299(5881):365–367. doi: 10.1038/299365a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Glickman B. W., Rietveld K., Aaron C. S. gamma-Ray induced mutational spectrum in the lacI gene of Escherichia coli: comparison of induced and spontaneous spectra at the molecular level. Mutat Res. 1980 Jan;69(1):1–12. doi: 10.1016/0027-5107(80)90171-2. [DOI] [PubMed] [Google Scholar]
  11. Hatayama T., Goldberg I. H. Deoxyribonucleic acid sugar damage in the action of neocarzinostatin. Biochemistry. 1980 Dec 9;19(25):5890–5898. doi: 10.1021/bi00566a035. [DOI] [PubMed] [Google Scholar]
  12. Hatayama T., Goldberg I. H., Takeshita M., Grollman A. P. Nucleotide specificity in DNA scission by neocarzinostatin. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3603–3607. doi: 10.1073/pnas.75.8.3603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ishida R., Takahashi T. In vitro release of thymine from DNA by neocarzinostatin. Biochem Biophys Res Commun. 1976 Jan 12;68(1):256–261. doi: 10.1016/0006-291x(76)90037-1. [DOI] [PubMed] [Google Scholar]
  14. Kappen L. S., Goldberg I. H. Gaps in DNA induced by neocarzinostatin bear 3'- and 5'-phosphoryl termini. Biochemistry. 1978 Feb 21;17(4):729–734. doi: 10.1021/bi00597a027. [DOI] [PubMed] [Google Scholar]
  15. Kappen L. S., Napier M. A., Goldberg I. H. Roles of chromophore and apo-protein in neocarzinostatin action. Proc Natl Acad Sci U S A. 1980 Apr;77(4):1970–1974. doi: 10.1073/pnas.77.4.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kumagai K., Ono Y., Nishikawa T., Ishida N. Cytological studies on the effect of neocarzinostatin on HeLa cells. J Antibiot (Tokyo) 1966 Mar;19(2):69–74. [PubMed] [Google Scholar]
  17. Napier M. A., Kappen L. S., Goldberg I. H. Effect of nonprotein chromophore removal on neocarzinostatin action. Biochemistry. 1980 Apr 29;19(9):1767–1773. doi: 10.1021/bi00550a007. [DOI] [PubMed] [Google Scholar]
  18. Ohtsuki K., Ishida N. Mechanism of DNA degradation induced by neocarzinostatin in Bacillus subtilis. J Antibiot (Tokyo) 1975 Mar;28(3):229–236. doi: 10.7164/antibiotics.28.229. [DOI] [PubMed] [Google Scholar]
  19. Ohtsuki K., Ishida N. Neocarzinostatin-induced breakdown of deoxyribonucleic acid in HeLa-S3 cells. J Antibiot (Tokyo) 1975 Feb;28(2):143–148. doi: 10.7164/antibiotics.28.143. [DOI] [PubMed] [Google Scholar]
  20. Poon R., Beerman T. A., Goldberg I. H. Characterization of DNA strand breakage in vitro by the antitumor protein neocarzinostatin. Biochemistry. 1977 Feb 8;16(3):486–493. doi: 10.1021/bi00622a023. [DOI] [PubMed] [Google Scholar]
  21. Povirk L. F., Goldberg I. H. Covalent adducts of DNA and the nonprotein chromophore of neocarzinostatin contain a modified deoxyribose. Proc Natl Acad Sci U S A. 1982 Jan;79(2):369–373. doi: 10.1073/pnas.79.2.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schmeissner U., Ganem D., Miller J. H. Genetic studies of the lac repressor. II. Fine structure deletion map of the lacI gene, and its correlation with the physical map. J Mol Biol. 1977 Jan 15;109(2):303–326. doi: 10.1016/s0022-2836(77)80036-3. [DOI] [PubMed] [Google Scholar]
  23. Takeshita M., Kappen L. S., Grollman A. P., Eisenberg M., Goldberg I. H. Strand scission of deoxyribonucleic acid by neocarzinostatin, auromomycin, and bleomycin: studies on base release and nucleotide sequence specificity. Biochemistry. 1981 Dec 22;20(26):7599–7606. doi: 10.1021/bi00529a039. [DOI] [PubMed] [Google Scholar]
  24. Tatsumi K., Nishioka H. Effect of DNA Repair systems on antibacterial and mutagenic activity of an antitumor protein, neocarzinostatin. Mutat Res. 1977 Apr;48(2):195–203. doi: 10.1016/0027-5107(77)90161-0. [DOI] [PubMed] [Google Scholar]
  25. VOGEL H. J., BONNER D. M. Acetylornithinase of Escherichia coli: partial purification and some properties. J Biol Chem. 1956 Jan;218(1):97–106. [PubMed] [Google Scholar]
  26. Witkin E. M. Ultraviolet mutagenesis and inducible DNA repair in Escherichia coli. Bacteriol Rev. 1976 Dec;40(4):869–907. doi: 10.1128/br.40.4.869-907.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]

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