Abstract
Sixteen species of enterobacteria have been screened for mutagenic DNA repair activity. In Escherichia coli, mutagenic DNA repair is encoded by the umuDC operon. Synthesis of UmuD and UmuC proteins is induced as part of the SOS response to DNA damage, and after induction, the UmuD protein undergoes an autocatalytic cleavage to produce the carboxy-terminal UmuD' fragment needed for induced mutagenesis. The presence of a similar system in other species was examined by using a combined approach of inducible-mutagenesis assays, cross-reactivity to E. coli UmuD and UmuD' antibodies to test for induction and cleavage of UmuD-like proteins, and hybridization with E. coli and Salmonella typhimurium umu DNA probes to map umu-like genes. The results indicate a more widespread distribution of mutagenic DNA repair in other species than was previously thought. They also show that umu loci can be more complex in other species than in E. coli. Differences in UV-induced mutability of more than 200-fold were seen between different species of enteric bacteria and even between multiple natural isolates of E. coli, and yet some of the species which display a poorly mutable phenotype still have umu-like genes and proteins. It is suggested that umDC genes can be curtailed in their mutagenic activities but that they may still participate in some other, unknown process which provides the continued stimulus for their retention.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- Bagg A., Kenyon C. J., Walker G. C. Inducibility of a gene product required for UV and chemical mutagenesis in Escherichia coli. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5749–5753. doi: 10.1073/pnas.78.9.5749. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Battista J. R., Ohta T., Nohmi T., Sun W., Walker G. C. Dominant negative umuD mutations decreasing RecA-mediated cleavage suggest roles for intact UmuD in modulation of SOS mutagenesis. Proc Natl Acad Sci U S A. 1990 Sep;87(18):7190–7194. doi: 10.1073/pnas.87.18.7190. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blanco M., Herrera G., Aleixandre V. Different efficiency of UmuDC and MucAB proteins in UV light induced mutagenesis in Escherichia coli. Mol Gen Genet. 1986 Nov;205(2):234–239. doi: 10.1007/BF00430433. [DOI] [PubMed] [Google Scholar]
- Burckhardt S. E., Woodgate R., Scheuermann R. H., Echols H. UmuD mutagenesis protein of Escherichia coli: overproduction, purification, and cleavage by RecA. Proc Natl Acad Sci U S A. 1988 Mar;85(6):1811–1815. doi: 10.1073/pnas.85.6.1811. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Donnelly C. E., Walker G. C. groE mutants of Escherichia coli are defective in umuDC-dependent UV mutagenesis. J Bacteriol. 1989 Nov;171(11):6117–6125. doi: 10.1128/jb.171.11.6117-6125.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dowden S. B., Strike P. R46-derived recombinant plasmids affecting DNA repair and mutation in E. coli. Mol Gen Genet. 1982;186(1):140–144. doi: 10.1007/BF00422926. [DOI] [PubMed] [Google Scholar]
- Elledge S. J., Walker G. C. Proteins required for ultraviolet light and chemical mutagenesis. Identification of the products of the umuC locus of Escherichia coli. J Mol Biol. 1983 Feb 25;164(2):175–192. doi: 10.1016/0022-2836(83)90074-8. [DOI] [PubMed] [Google Scholar]
- Elledge S. J., Walker G. C. The muc genes of pKM101 are induced by DNA damage. J Bacteriol. 1983 Sep;155(3):1306–1315. doi: 10.1128/jb.155.3.1306-1315.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Freitag N., McEntee K. "Activated"-RecA protein affinity chromatography of LexA repressor and other SOS-regulated proteins. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8363–8367. doi: 10.1073/pnas.86.21.8363. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HOWARD-FLANDERS P., SIMSON E., THERIOT L. A LOCUS THAT CONTROLS FILAMENT FORMATION AND SENSITIVITY TO RADIATION IN ESCHERICHIA COLI K-12. Genetics. 1964 Feb;49:237–246. doi: 10.1093/genetics/49.2.237. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Herrera G., Urios A., Aleixandre V., Blanco M. UV-light-induced mutability in Salmonella strains containing the umuDC or the mucAB operon: evidence for a umuC function. Mutat Res. 1988 Mar;198(1):9–13. doi: 10.1016/0027-5107(88)90034-6. [DOI] [PubMed] [Google Scholar]
- Hiom K., Thomas S. M., Sedgwick S. G. Different mechanisms for SOS induced alleviation of DNA restriction in Escherichia coli. Biochimie. 1991 Apr;73(4):399–405. doi: 10.1016/0300-9084(91)90106-b. [DOI] [PubMed] [Google Scholar]
- Hofemeister J., Köhler H., Filippov V. D. DNA repair in Proteus mirabilis. VI. Plasmid (R46-) mediated recovery and UV mutagenesis. Mol Gen Genet. 1979 Oct 3;176(2):265–273. [PubMed] [Google Scholar]
- Hughes V. M., Datta N. Conjugative plasmids in bacteria of the 'pre-antibiotic' era. Nature. 1983 Apr 21;302(5910):725–726. doi: 10.1038/302725a0. [DOI] [PubMed] [Google Scholar]
- Kato T., Shinoura Y. Isolation and characterization of mutants of Escherichia coli deficient in induction of mutations by ultraviolet light. Mol Gen Genet. 1977 Nov 14;156(2):121–131. doi: 10.1007/BF00283484. [DOI] [PubMed] [Google Scholar]
- Kitagawa Y., Akaboshi E., Shinagawa H., Horii T., Ogawa H., Kato T. Structural analysis of the umu operon required for inducible mutagenesis in Escherichia coli. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4336–4340. doi: 10.1073/pnas.82.13.4336. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lehrbach P. R., Lee B. T., Dirckze C. D. Effect of repair deficiency and R plasmids on spontaneous and radiation-induced mutability in Pseudomonas aeruginosa. J Bacteriol. 1979 Sep;139(3):953–960. doi: 10.1128/jb.139.3.953-960.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Little J. W. Autodigestion of lexA and phage lambda repressors. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1375–1379. doi: 10.1073/pnas.81.5.1375. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lodwick D., Owen D., Strike P. DNA sequence analysis of the imp UV protection and mutation operon of the plasmid TP110: identification of a third gene. Nucleic Acids Res. 1990 Sep 11;18(17):5045–5050. doi: 10.1093/nar/18.17.5045. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lovett C. M., Jr, Love P. E., Yasbin R. E., Roberts J. W. SOS-like induction in Bacillus subtilis: induction of the RecA protein analog and a damage-inducible operon by DNA damage in Rec+ and DNA repair-deficient strains. J Bacteriol. 1988 Apr;170(4):1467–1474. doi: 10.1128/jb.170.4.1467-1474.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MacPhee D. G. Spontaneous, ultraviolet and ionizing radiation mutagenesis in two auxotrophic strains of Salmonella typhimurium carrying an R plasmid. Mutat Res. 1977 Oct;45(1):1–6. doi: 10.1016/0027-5107(77)90036-7. [DOI] [PubMed] [Google Scholar]
- Marsh L., Walker G. C. Cold sensitivity induced by overproduction of UmuDC in Escherichia coli. J Bacteriol. 1985 Apr;162(1):155–161. doi: 10.1128/jb.162.1.155-161.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McCann J., Spingarn N. E., Kobori J., Ames B. N. Detection of carcinogens as mutagens: bacterial tester strains with R factor plasmids. Proc Natl Acad Sci U S A. 1975 Mar;72(3):979–983. doi: 10.1073/pnas.72.3.979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miller R. V., Kokjohn T. A. General microbiology of recA: environmental and evolutionary significance. Annu Rev Microbiol. 1990;44:365–394. doi: 10.1146/annurev.mi.44.100190.002053. [DOI] [PubMed] [Google Scholar]
- Misuraca F., Rampolla D., Grimaudo S. Identification and cloning of a umu locus in Streptomyces coelicolor A3(2). Mutat Res. 1991 Mar;262(3):183–188. doi: 10.1016/0165-7992(91)90020-5. [DOI] [PubMed] [Google Scholar]
- Mortelmans K. E., Stocker B. A. Ultraviolet light protection, enhancement of ultraviolet light mutagenesis, and mutator effect of plasmid R46 in Salmonella typhimurium. J Bacteriol. 1976 Oct;128(1):271–282. doi: 10.1128/jb.128.1.271-282.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nohmi T., Battista J. R., Dodson L. A., Walker G. C. RecA-mediated cleavage activates UmuD for mutagenesis: mechanistic relationship between transcriptional derepression and posttranslational activation. Proc Natl Acad Sci U S A. 1988 Mar;85(6):1816–1820. doi: 10.1073/pnas.85.6.1816. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nohmi T., Hakura A., Nakai Y., Watanabe M., Murayama S. Y., Sofuni T. Salmonella typhimurium has two homologous but different umuDC operons: cloning of a new umuDC-like operon (samAB) present in a 60-megadalton cryptic plasmid of S. typhimurium. J Bacteriol. 1991 Feb;173(3):1051–1063. doi: 10.1128/jb.173.3.1051-1063.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Orrego C., Eisenstadt E. An inducible pathway is required for mutagenesis in Salmonella typhimurium LT2. J Bacteriol. 1987 Jun;169(6):2885–2888. doi: 10.1128/jb.169.6.2885-2888.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Perry K. L., Elledge S. J., Mitchell B. B., Marsh L., Walker G. C. umuDC and mucAB operons whose products are required for UV light- and chemical-induced mutagenesis: UmuD, MucA, and LexA proteins share homology. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4331–4335. doi: 10.1073/pnas.82.13.4331. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Roca A. I., Cox M. M. The RecA protein: structure and function. Crit Rev Biochem Mol Biol. 1990;25(6):415–456. doi: 10.3109/10409239009090617. [DOI] [PubMed] [Google Scholar]
- Sedgwick S. G., Goodwin P. A. Differences in mutagenic and recombinational DNA repair in enterobacteria. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4172–4176. doi: 10.1073/pnas.82.12.4172. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sedgwick S. G., Goodwin P. A. Interspecies regulation of the SOS response by the E. coli lexA+ gene. Mutat Res. 1985 May;145(3):103–106. doi: 10.1016/0167-8817(85)90015-x. [DOI] [PubMed] [Google Scholar]
- Sedgwick S. G. Inducible DNA repair in microbes. Microbiol Sci. 1986 Mar;3(3):76-8, 83. [PubMed] [Google Scholar]
- Sedgwick S. G., Robson M., Malik F. Polymorphisms in the umuDC region of Escherichia species. J Bacteriol. 1988 Apr;170(4):1610–1616. doi: 10.1128/jb.170.4.1610-1616.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shinagawa H., Iwasaki H., Kato T., Nakata A. RecA protein-dependent cleavage of UmuD protein and SOS mutagenesis. Proc Natl Acad Sci U S A. 1988 Mar;85(6):1806–1810. doi: 10.1073/pnas.85.6.1806. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shinagawa H., Kato T., Ise T., Makino K., Nakata A. Cloning and characterization of the umu operon responsible for inducible mutagenesis in Escherichia coli. Gene. 1983 Aug;23(2):167–174. doi: 10.1016/0378-1119(83)90048-3. [DOI] [PubMed] [Google Scholar]
- Skavronskaya A. G., Stepanova N. F., Andreeva I. V. UV-mutable hybrids of Salmonella incorporating Escherichia coli region adjacent to tryptophan operon. Mol Gen Genet. 1982;185(2):315–318. doi: 10.1007/BF00330804. [DOI] [PubMed] [Google Scholar]
- Slilaty S. N., Little J. W. Lysine-156 and serine-119 are required for LexA repressor cleavage: a possible mechanism. Proc Natl Acad Sci U S A. 1987 Jun;84(12):3987–3991. doi: 10.1073/pnas.84.12.3987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Slilaty S. N., Rupley J. A., Little J. W. Intramolecular cleavage of LexA and phage lambda repressors: dependence of kinetics on repressor concentration, pH, temperature, and solvent. Biochemistry. 1986 Nov 4;25(22):6866–6875. doi: 10.1021/bi00370a020. [DOI] [PubMed] [Google Scholar]
- Smith C. M., Eisenstadt E. Identification of a umuDC locus in Salmonella typhimurium LT2. J Bacteriol. 1989 Jul;171(7):3860–3865. doi: 10.1128/jb.171.7.3860-3865.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith C. M., Koch W. H., Franklin S. B., Foster P. L., Cebula T. A., Eisenstadt E. Sequence analysis and mapping of the Salmonella typhimurium LT2 umuDC operon. J Bacteriol. 1990 Sep;172(9):4964–4978. doi: 10.1128/jb.172.9.4964-4978.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Steinborn G. Uvm mutants of Escherichia coli K12 deficient in UV mutagenesis. I. Isolation of uvm mutants and their phenotypical characterization in DNA repair and mutagenesis. Mol Gen Genet. 1978 Sep 20;165(1):87–93. doi: 10.1007/BF00270380. [DOI] [PubMed] [Google Scholar]
- Strike P., Lodwick D. Plasmid genes affecting DNA repair and mutation. J Cell Sci Suppl. 1987;6:303–321. doi: 10.1242/jcs.1984.supplement_6.20. [DOI] [PubMed] [Google Scholar]
- Thomas S. M., Crowne H. M., Pidsley S. C., Sedgwick S. G. Structural characterization of the Salmonella typhimurium LT2 umu operon. J Bacteriol. 1990 Sep;172(9):4979–4987. doi: 10.1128/jb.172.9.4979-4987.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thomas S. M., Sedgwick S. G. Cloning of Salmonella typhimurium DNA encoding mutagenic DNA repair. J Bacteriol. 1989 Nov;171(11):5776–5782. doi: 10.1128/jb.171.11.5776-5782.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Witkin E. M., Roegner-Maniscalco V., Sweasy J. B., McCall J. O. Recovery from ultraviolet light-induced inhibition of DNA synthesis requires umuDC gene products in recA718 mutant strains but not in recA+ strains of Escherichia coli. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6805–6809. doi: 10.1073/pnas.84.19.6805. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Woodgate R., Rajagopalan M., Lu C., Echols H. UmuC mutagenesis protein of Escherichia coli: purification and interaction with UmuD and UmuD'. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7301–7305. doi: 10.1073/pnas.86.19.7301. [DOI] [PMC free article] [PubMed] [Google Scholar]