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. 1972 Feb;109(2):475–483. doi: 10.1128/jb.109.2.475-483.1972

Deoxyribonucleic Acid Damage by Monofunctional Mitomycins and Its Repair in Escherichia coli

Nozomu Otsuji 1, Ichiko Murayama 1
PMCID: PMC285165  PMID: 4550809

Abstract

Exposure of Escherichia coli to the antibiotic mitomycin C (MTC) at a concentration of 0.5 μg/ml caused cross-linkage between complementary strands of deoxyribonucleic acid (DNA). Derivatives of mitomycin, 7-methoxymitosene (7-MMT) and decarbamoyl mitomycin C (DCMTC), at a level as high as 20 μg/ml formed no cross-links between DNA strands. Ultraviolet light-sensitive mutants of E. coli K-12 bearing uvrA, uvrB, uvrC, or recA mutations were more sensitive to the lethal action of 7-MMT and of DCMTC than was the wild-type strain. Treatment of wild-type cells with these antibiotics resulted in the production of single-strand breaks in DNA, which were repaired upon incubation in a growth medium. Such breaks in DNA were not produced in the uvrA and the uvrB mutants. In the uvrC mutant, single-strand breaks were produced by 7-MMT or by DCMTC, but these breaks were not repaired upon incubation. These results are discussed in connection with the mechanism for removal of pyrimidine dimers in ultraviolet-irradiated bacteria.

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Selected References

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

  1. Allen G. R., Jr, Poletto J. F., Weiss M. J. The mitomycin antibiotics. Synthetic studies. V. Preparation of 7-methoxymitosene. J Org Chem. 1965 Sep;30(9):2897–2904. doi: 10.1021/jo01020a006. [DOI] [PubMed] [Google Scholar]
  2. BOYCE R. P., HOWARD-FLANDERS P. GENETIC CONTROL OF DNA BREAKDOWN AND REPAIR IN E. COLI K-12 TREATED WITH MITOMYCIN C OR ULTRAVIOLET LIGHT. Z Vererbungsl. 1964 Dec 30;95:345–350. doi: 10.1007/BF01268667. [DOI] [PubMed] [Google Scholar]
  3. BOYCE R. P., HOWARD-FLANDERS P. RELEASE OF ULTRAVIOLET LIGHT-INDUCED THYMINE DIMERS FROM DNA IN E. COLI K-12. Proc Natl Acad Sci U S A. 1964 Feb;51:293–300. doi: 10.1073/pnas.51.2.293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brookes P., Lawley P. D. The reaction of mono- and di-functional alkylating agents with nucleic acids. Biochem J. 1961 Sep;80(3):496–503. doi: 10.1042/bj0800496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. GREENBERG J., MANDELL J. D., WOODY P. L. Resistance and cross-resistance of Escherichia coli mutants to antitumour agent mitomycin C. J Gen Microbiol. 1961 Nov;26:509–520. doi: 10.1099/00221287-26-3-509. [DOI] [PubMed] [Google Scholar]
  6. HATA T., HOSHI T., KANAMORI K., MATSUMAE A., SANO Y., SHIMA T., SUGAWARA R. Mitomycin, a new antibiotic from Streptomyces. I. J Antibiot (Tokyo) 1956 Jul;9(4):141–146. [PubMed] [Google Scholar]
  7. Howard-Flanders P. DNA repair. Annu Rev Biochem. 1968;37:175–200. doi: 10.1146/annurev.bi.37.070168.001135. [DOI] [PubMed] [Google Scholar]
  8. IYER V. N., SZYBALSKI W. A MOLECULAR MECHANISM OF MITOMYCIN ACTION: LINKING OF COMPLEMENTARY DNA STRANDS. Proc Natl Acad Sci U S A. 1963 Aug;50:355–362. doi: 10.1073/pnas.50.2.355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. IYER V. N., SZYBALSKI W. MITOMYCINS AND PORFIROMYCIN: CHEMICAL MECHANISM OF ACTIVATION AND CROSS-LINKING OF DNA. Science. 1964 Jul 3;145(3627):55–58. doi: 10.1126/science.145.3627.55. [DOI] [PubMed] [Google Scholar]
  10. Kinoshita S., Uzu K., Nakano K., Shimizu M., Takahashi T. Mitomycin derivatives. 1. Preparation of mitosane and mitosene compounds and their biological activities. J Med Chem. 1971 Feb;14(2):103–109. doi: 10.1021/jm00284a005. [DOI] [PubMed] [Google Scholar]
  11. Kinoshita S., Uzu K., Nakano K., Takahashi T. Mitomycin derivatives. 2. Derivatives of decarbamoylmitosane and decarbamoylmitosene. J Med Chem. 1971 Feb;14(2):109–112. doi: 10.1021/jm00284a006. [DOI] [PubMed] [Google Scholar]
  12. LEVINE M. Effect of mitomycin C on interactions between temperate phages and bacteria. Virology. 1961 Apr;13:493–499. doi: 10.1016/0042-6822(61)90280-x. [DOI] [PubMed] [Google Scholar]
  13. McGrath R. A., Williams R. W. Reconstruction in vivo of irradiated Escherichia coli deoxyribonucleic acid; the rejoining of broken pieces. Nature. 1966 Oct 29;212(5061):534–535. doi: 10.1038/212534a0. [DOI] [PubMed] [Google Scholar]
  14. OTSUJI N., SEKIGUCHI M., IIJIMA T., TAKAGI Y. Induction of phage formation in the lysogenic Escherichia coli K-12 by mitomycin C. Nature. 1959 Oct 3;184(Suppl 14):1079–1080. doi: 10.1038/1841079b0. [DOI] [PubMed] [Google Scholar]
  15. OTSUJI N. The effect of glucose on the induction of lambda phage formation by mitomycin C. Biken J. 1961 Dec;4:235–241. [PubMed] [Google Scholar]
  16. Otsuji N. Properties of mitomycin C-sensitive mutants of Escherichia coli K-12. J Bacteriol. 1968 Feb;95(2):540–545. doi: 10.1128/jb.95.2.540-545.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Prakash L., Strauss B. Repair of alkylation damage: stability of methyl groups in Bacillus subtilis treated with methyl methanesulfonate. J Bacteriol. 1970 Jun;102(3):760–766. doi: 10.1128/jb.102.3.760-766.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Reiter H., Strauss B. Repair of damage induced by a monofunctional alkylating agent in a transformable, ultraviolet-sensitive strain of Bacillus subtilis. J Mol Biol. 1965 Nov;14(1):179–194. doi: 10.1016/s0022-2836(65)80239-x. [DOI] [PubMed] [Google Scholar]
  19. SETLOW R. B., CARRIER W. L. THE DISAPPEARANCE OF THYMINE DIMERS FROM DNA: AN ERROR-CORRECTING MECHANISM. Proc Natl Acad Sci U S A. 1964 Feb;51:226–231. doi: 10.1073/pnas.51.2.226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. SHIBA S., TERAWAKI A., TAGUCHI T., KAWAMATA J. Selective inhibition of formation of deoxyribonucleic acid in Escherichia coli by mitomycin C. Nature. 1959 Apr 11;183(4667):1056–1057. doi: 10.1038/1831056a0. [DOI] [PubMed] [Google Scholar]
  21. SUGIURA K. Studies in a tumor spectrum. VIII. The effect of mitomycin C on the growth of a variety of mouse, rat, and hamster tumors. Cancer Res. 1959 May;19(4):438–445. [PubMed] [Google Scholar]
  22. Searashi T., Strauss B. Relation of the repair of damage induced by a monofunctional alkylating agent to the repair of damage induced by ultraviolet light in Bacillus subtilis. Biochem Biophys Res Commun. 1965 Sep 22;20(6):680–687. doi: 10.1016/0006-291x(65)90069-0. [DOI] [PubMed] [Google Scholar]
  23. Terawaki A., Greenberg J. Post-treatment breakage of mitomycin C induced cross-links in deoxyribonucleic acid of Escherichia coli. Biochim Biophys Acta. 1966 Jun 22;119(3):540–546. doi: 10.1016/0005-2787(66)90130-4. [DOI] [PubMed] [Google Scholar]

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