Summary
The DNA polymerase deficient mutantE. coli P3478polA1 is extremely sensitive to the lethal action of N-methyl-N′-nitro-N-nitrosoguanidine (NG) and methyl-methanesulfonate (MMS). ThepolA1 mutant has an almost unaffected mutability induced by NG or MMS and shows reduced ability to propagate MMS-treated phage T7. NG and MMS induce marked breakdown of DNA and inhibit significantly DNA synthesis in thepolA1 mutant. The obtained results suggest the thepolA1 mutant is unable to repair single-strand breaks of DNA induced by monofunctional alkylating agents. The suggestion is confirmed by the demonstrated sensitivity of thepolA1 mutant to thymine starvation (TS).
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Davis, B. D., Mingioli, E. S.: Mutants ofEscherichia coli requiring methionine or vitamin B12. J. Bact.60, 17–28 (1950).
Freese, E., Freese, E. B.: Mutagenic and inactivating DNA alterations. Radiat. Res., Suppl.6, 97–140 (1966).
Freifelder, D.: Single-strand breaks in bacterial DNA associated with thymine starvation. J. molec. Biol.45, 1–8 (1969).
Friedberg, E. C., Goldtwait, D. A.: Endonuclease II ofE. coli. Cold Spr. Harb. Symp. quant. Biol.33, 271–275 (1968).
Gross, J., Gross, M.: Genetic analysis of anE. coli strain with a mutation affecting DNA polymerase. Nature (Lond.)224, 1166–1168 (1969).
Haskel, E. H., Davern, C. I.: Pre-fork synthesis: a model for DNA replication. Proc. nat. Acad. Sci. (Wash.)64, 1065–1071 (1969).
Kanner, L., Hanawalt, P.: Repair deficiency in a bacterial mutant defective in DNA polymerase. Biochem. biophys. Res. Commun.39, 149–156 (1970).
Kelly, R. B., Atkinson, M. K., Huberman, J. A., Kornberg, A.: Excision of thymine dimers and other mismatched sequences by DNA polymerase ofEscherichia coli. Nature (Lond.)224, 495–501 (1969).
—, Cozzarelli, N. R., Deutscher, M. P., Lehman, I. R., Kornberg, A.: Enzymatic synthesis of deoxyribonucleic acid. XXXII. Replication of duplex deoxyribonucleic acid by polymerase at a single strand break. J. biol. Chem.245, 39–45 (1970)
Krieg, D. R.: Ethyl methanesulfonate-induced reversion of bacteriophage T4 rII mutants. Genetics48, 561–580 (1963).
Lawley, P. D., Brookes, P.: Acidic dissociation of 7:9-dialkylguanines and its possible relation to mutagenic properties of alkylating agents. Nature (Lond.)192, 1081–1082 (1961).
Loveless, A.: Possible relevance of 0–6 alkylation of deoxyguanosine to the mutagenicity and carcinogenicity of nitrosamines and nitrosamides. Nature (Lond.)223, 206–207 (1969).
Lucia, P. de, Cairns, J.: Isolation of anE. coli strain with a mutation affecting DNA polymerase. Nature (Lond.)224, 1164–1166 (1969).
Nagata, C., Imamura, A., Sato, H., Fukui, K.: Changes in π-electron distribution of deoxyribonucleic acid after alkylation and their possible relation to the biological effect. Gann54, 109–117 (1963).
Reiter, H., Strauss, B.: Rpair of damage induced by a monofunctional alkylating agent in a transformable, ultraviolet-sensitive strain ofBacillus subtilis. J. molec. Biol.14, 179–194 (1965).
——, Robbins, M., Marone, R.: Nature of the repair of methyl methanesulfonate-induced damage inBacillus subtilis. J. Bact.93, 1056–1062 (1967).
Rhaese, H. J., Freese, E.: Chemical analysis of DNA alterations. IV. Reaction of oligodeoxynucleotides with monofunctional alkylating agents leading to backbone breakage. Biochim. biophys. Acta (Amst.)190, 418–433 (1969).
Smirnow, G. B., Favorskaya, Yu. N.: The system ofE. coli K-12 which repair DNA alterations induced by monofunctional alkylating agents. Symp. “Molecular basis of genetic processes” Abstracts. Moscow (1970).
—, Skavronskaya, A. G.: On the repair of damages induced by N-methyl-N′-nitro-N-nitrosoguanidine in the bacterial DNA. Genetika (USSR)4, 111–115 (1968).
Strauss, B. S.: Differential destruction of the transforming activity of damaged deoxyribonucleic acid by a bacterial enzyme. Proc. nat. Acad. Sci. (Wash.)48, 1670–1675 (1962).
—, Coyle, M., Robbins, M.: Alkylation damage and its repair. Cold Spr. Harb. Symp. quant. Biol.33, 277–288 (1968).
—, Reiten, H., Searashi, T.: Recover from ultraviolet- and alkylating agent-induced damage inBacillus subtilis. Radiat. Res., Suppl.6, 201–211 (1966).
Witkin, E. M.: Mutation-proof and mutation-prone modes of survival in derivatives ofEscherichia coli B differing in sensitivity to ultraviolet light. Brookhaven Symp.20, 17–55 (1967).
Author information
Authors and Affiliations
Additional information
Communicated by H. Böhme
Rights and permissions
About this article
Cite this article
Smirnov, G.B., Favorskaya, Y.N. & Skavronskaya, A.G. Monofunctional alkylating agent-induced inactivation, mutagenesis and DNA degradation in anEscherichia coli mutant deficient in DNA polymerase. Molec. Gen. Genet. 111, 357–367 (1971). https://doi.org/10.1007/BF00569788
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00569788