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Journal of Bacteriology, July 2005, p. 5044-5048, Vol. 187, No. 14
0021-9193/05/$08.00+0     doi:10.1128/JB.187.14.5044-5048.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Mutator Effects in Escherichia coli Caused by the Expression of Specific Foreign Genes

Vanessa Gabrovsky, Mitsuko Lynn Yamamoto, and Jeffrey H. Miller*

Department of Microbiology, Immunology, and Molecular Genetics and The Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California 90095

Received 24 January 2005/ Accepted 14 April 2005


   ABSTRACT
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Certain genes from Lactococcus lactis and Pseudomonas aeruginosa, including the nfxB gene, generate a mutator phenotype in Escherichia coli. The results of this study, together with those of a previous study, support conservation of regulatory sequences in E. coli and P. aeruginosa and suggest that some efflux pumps prevent mutagenicity by exporting mutagenic products of metabolism.


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Understanding mutational pathways and the repair systems that operate on them has proved to be important in elucidating the nature of a number of human diseases, including cancer (for instance, for reviews, see references 17 and 22). The discovery of genes involved in mutagenesis and repair has frequently depended on mutational analysis, and often this involves looking for genes that when inactivated result in a mutator (increased mutagenesis) phenotype (for reviews, see references 29 and 30). For example, in Escherichia coli the inactivation of either the dam, mutS, mutL, mutH, or uvrD gene leads to loss of the mismatch repair system (13, 26, 34) and loss of the mutY or mutM gene leads to reduced capacity to repair oxidative damage to DNA (5, 27, 35). The human counterparts to mutS, mutL, mutY, and mutM (ogg-1) have been characterized (2, 38, 44; for reviews, see references 9, 21, and 32), and loss of the mismatch repair system or the MutY repair capacity leads to increased cancer susceptibilities in humans (1, 20). Defining additional genes involved in mutagenesis is therefore of great interest. New approaches may lead to novel mutational pathways. Recently, using a random shotgun cloning approach, we have identified 15 genes in E. coli that when cloned onto a multicopy plasmid result in a mutator phenotype (45). Twelve of these were not previously known to cause a mutator phenotype when overexpressed. One gene previously shown to increase mutagenesis when overexpressed (8) was not detected in our study. A striking finding from this work is that overexpression of the emrR gene, involved in regulating the EmrAB multidrug resistance pump (25; emr signifying E. coli multidrug resistance [24]), leads to greatly increased mutagenesis (45). We have extended this approach by looking for genes from foreign DNA that result in increased mutagenesis when cloned into E. coli on a multicopy plasmid. This analysis might not only identify potential mutational pathways in E. coli by finding genes whose counterparts did not show up in the original study but can also allow the dissection of mutagenic and repair pathways in microorganisms that do not have developed genetic systems that provide mutator screens. In the work reported here, we identify a set of genes from Lactococcus lactis that result in a mutagenic response in E. coli. We also find that only one gene from the opportunistic pathogen Pseudomonas aeruginosa generates a detectable mutagenic effect when cloned onto a specific multicopy plasmid in E. coli. This gene, the nfxB gene (nfx signifying resistance to norfloxacin [19]), is a regulator of one of the P. aeruginosa multidrug resistance pumps (37; for a review, see also reference 16) and one of the functional counterparts of the E. coli emrR gene, thus extending the association of multidrug resistance pumps and mutagenesis.

We prepared DNA from either L. lactis or P. aeruginosa (ATCC 4109 or ATCC 51007, respectively) and partially digested it with restriction enzyme Sau3AI. We isolated DNA fragments 3 to 5 kilobases in length from an agarose gel and ligated them into the BamHI site of vector pCR2.1-TOPOCam (45), a derivative of multicopy vector pCR2.1-TOPO (Invitrogen, Carlsbad, CA), constructed by inserting a gene conferring chloramphenicol resistance at the PCR cloning site and by eliminating a 1.6-kb PstI fragment (45). These random shotgun-generated genomic DNA libraries were electroporated into the E. coli frameshift tester strain CC107 [ara {Delta}(gpt-lac)5 thi/F'128 lacIZ proA+B+ (6)]. It carries a frameshift mutation in lacZ on the F' plasmid that reverts only by insertion of a G in a run of six G's. The electrotransformants were directly plated on glucose minimal medium supplemented with phenyl-ß-D-galactoside (P-Gal) and 5-bromo-4-chloro-3-indolyl-ß-D-galactoside (X-Gal) as previously described (35, 45). After 4 days of incubation at 37°C, the frameshift mutator candidates were identified as colonies that contained elevated levels of blue papillae, microcolonies growing out from the surface of the agar. Purified colonies were used to prepare plasmid DNA to retransform CC107, to verify that the mutator phenotype was caused by DNA on the plasmid. We estimated the insert size of each plasmid by agarose gel electrophoresis using a supercoiled DNA ladder as a standard (Invitrogen, Carlsbad, CA). We sequenced the 3' and 5' ends of each insert using two vector primers, 5'-CAGGAAACAGCTATGAC-3' and 5'-TGGCAGAAATTCGATGATAAGCT-3', and identified each insert by BLAST analysis against the annotated genome sequence of L. lactis (3) and P. aeruginosa (39).

We screened approximately 100,000 transformants and identified 11 inserts from L. lactis and 25 from P. aeruginosa that gave mutator phenotypes. Figure 1 shows the distribution of the inserts on the L. lactis and P. aeruginosa annotated genome maps. The inserts range in size from 0.7 kb to 4.6 kb and are derived from four regions on the L. lactis genome, representing eight distinct insert types, and only one region of the P. aeruginosa genome, representing two distinct insert types, from at least five independent occurrences, among the 25 isolates.



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  		FIG. 1. Distribution of inserts from L. lactis and P. aeruginosa yielding mutator effects in E. coli. The letters B, D, and E for nfxB refer to independent experiments.

 
To quantify the results of plate mutator assays, we determined the Rifr (base substitution) and Lac+ (frameshift) frequencies in liquid culture (31). All bacterial genetic methods were carried out as described previously by Miller (28). Table 1 shows the mutation frequency resulting from each cloned insert. E. coli CC107 measures +1 frameshifts, as mentioned above, and the isogenic strain, CC108 (6), measures –1 frameshifts, since the F' plasmid carries a lacZ mutation that reverts by the loss of a G from a run of six G's. The largest mutagenic effect is seen with the inserts from P. aeruginosa, all of which contain the nfxB gene. The smaller inserts with only the nfxB gene give up to a 600-fold increase for the +1 frameshift and a 170-fold increase (higher in this case for the larger insert) for the –1 frameshift. The nfxB insert in P. aeruginosa PAO1 B1 results in a significant increase (43-fold) for the base substitutions measured by the Rifr assay.


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  		TABLE 1. Frequencies of mutations in E. coli CC107 carrying plasmids with different inserts

 
The inserts from the L. lactis genome reveal four regions that generate mutator effects when cloned into E. coli. By examining the length of DNA in each clone, we can pinpoint the gene responsible without further experiments in three cases, dnaA, uvrA, and pi228. The fourth region involves three genes, rnhA, sipL, and purR. Cloning smaller regions by using designed oligonucleotides as PCR primers allows us to examine the effect of an insert containing only rnhA and sipL but lacking purR, as well as inserts containing either rnhA alone or sipL alone. For cloning, we used the following oligonucleotides to prime PCRs for the following genes and species: for rnhA (L. lactis), 5'-ATTGGTACTAGTTATTGATTGTGAGTTGGTCGTG and 5'-CTATACGAGCTCCTGATGAACCGACCGCAAGT; for sipL (L. lactis), 5'-AATCCGGAGCTCATACACAAAAAGCGATTA and 5'-ATTATTACTAGTGAGAACGATTGATTGATGAT; for dnaA (E. coli), 5'-ATCTACGAGCTCTATCCGCGAAAAATGAAAC and 5'-TCCGTAACTAGTCTGGGTCGCTTCAATTCA; for rnhA (E. coli), 5'-ATAAGTGAGCTCTGCCTGACGTACAATGCG and 5'-AAACGAACTAGTAAACTTGTGCCGGTATTG; for uvrA (E. coli), 5'-CAATAAGAGCTCCTGAATAAGTGTTAAACG and 5'-TCTTATACTAGTTCTGGTGGATGCGTCTTA.

The purified product was digested with SacI and SpeI to cleave at sites programmed into the sequence. The digestion mix was ligated into the Topo4 vector that had been cut with the same enzymes, and the ligation product was transformed into E. coli CC107 and plated on X-Gal P-Gal glucose plates with chloramphenicol. Mutator colonies were then analyzed further. From the results shown in Table 1, it is evident that the gene responsible for the mutator effect is rnhA. The effects of all four regions are significant but not as strong as those seen for the P. aeruginosa nfxB gene (Table 1; see below), which stimulates both base substitutions and frameshifts.

Although the dnaA, uvrA, and rnhA genes have homologous counterparts in E. coli, an extensive search for E. coli genes that generate mutator effects when overexpressed failed to detect either of these three genes (45). We therefore cloned each of these three genes from E. coli, using methods described above, and inserted each of them into the overexpressing vector. As Table 2 shows, in two cases, uvrA and rnhA, the E. coli gene did not cause a mutator phenotype, whereas the L. lactis gene did (Table 1). The dnaA gene did give a mutator effect, so we can add this gene to the list of these found in E. coli. Given that the effect is weak and a large number of mutator clones containing other inserts were present in the E. coli experiment (45), it is not unreasonable that dnaA and perhaps several other genes escaped detection.


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  		TABLE 2. Frequencies of mutations resulting from cloned E. coli genes

 
Table 3 summarizes the findings of this study that tested foreign genes from two different microorganisms for their mutator effects when the genes were overexpressed in E. coli. (All of these overexpressing clones were also tested in a recA host, and with the exception of the clone carrying pi228, the mutator effects were not significantly reduced [data not shown].) The only gene we detected from P. aeruginosa that gave an effect was the nfxB gene. We found nfxB in 25 clones from several experiments. Overexpressing this gene gave a 620-fold increase in +1 frameshifts and a 43-fold increase in base substitutions. It is striking that expressing a Pseudomonas aeruginosa regulator can have such a large effect in E. coli. The NfxB protein regulates the mex operon that encodes a multidrug resistance pump in P. aeruginosa (Fig. 2A). In our previous study (45), we reported that overexpressing the E. coli EmrR protein caused a significant mutagenic effect, increasing frameshifts by 4,000-fold and base substitutions by 125-fold. This protein is the regulator for an E. coli multidrug resistance pump (Fig. 2B). An analysis of the base substitution mutations in rpoB in E. coli CC107 induced by overexpressing each of these genes showed a virtually identical spectrum (45; unpublished data) that is diagnostic for replication errors (12, 31). Clearly, there is a mutational pathway that is revealed by the overexpression of either of these regulatory proteins, even when one of them is a foreign gene, and that involves increasing replication errors. How the signal is transduced from these proteins to the cellular replication machinery is the focus of continuing work. One intriguing possibility is that the failure to synthesize several multidrug resistance pumps, a consequence of overproduction of a common repressor, prevents the elimination of mutagenic intermediates generated in the normal biosynthesis and metabolism of purines and pyrimidines. At some critical concentration these compounds might act as base analog mutagens. There are indications that some of the efflux protein pumps may have evolved to reduce toxic levels of metabolic intermediates (4, 18, 43). We postulate that several pumps under the control of the EmrR repressor in E. coli are required to eliminate mutagenic intermediates when their concentration exceeds a certain threshold. The overexpression of the P. aeruginosa NfxB protein would have the same effect because it would recognize the same operators to some degree. There is precedent for this, as exemplified by the recent finding that the E. coli nitric oxide sensor NorR recognizes a conserved target sequence in diverse proteobacteria, including P. aeruginosa (42). There are also precedents for a common regulator of multiple efflux pumps (16, 41). For instance, in Staphylococcus aureus the MgrA protein regulates the NorA efflux pump (40), as well as the NorB and Tet38 efflux transporters (40).


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  		TABLE 3. Summary of effects of inserts on mutation frequencies in E. coli

 


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  		FIG. 2. Regulation of multidrug resistance pumps in P. aeruginosa and E. coli. (A) The nfxB gene encodes a repressor for the mexCD-oprJ operon in P. aeruginosa (adapted from reference 16). (B) The emrR gene encodes a repressor for the emrAB operon in E. coli.

 
Interestingly, at least one UvrA homolog, DrrC from Streptomyces peucetius, is involved in drug resistance, in this case resistance to daunorubicin, either by binding to DNA or by stimulating a specific efflux system (11, 23). Thus, the drrC gene, when expressed in a uvrA derivative of E. coli, confers daunorubicin resistance. It is not clear whether the L. lactis uvrA gene detected in this study plays such a role.


   ACKNOWLEDGMENTS
 
We thank Hanjing Yang for advice and discussions.

This work was supported by a grant from the National Institutes of Health (ES 0110875).


   FOOTNOTES
 
* Corresponding author. Mailing address: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, 405 Hilgard Ave., Los Angeles, CA 90095. Phone: (310) 825-8460. Fax: (310) 206-3088. E-mail: jhmiller{at}mbi.ucla.edu. Back


   REFERENCES
Top
 Abstract
 Text
 References
 

  1. Al-Tassan, N., N. H. Chmiel, J. Maynard, N. Fleming, A. L. Livingston, G. T. Williams, A. K. Hodges, D. R. Davies, S. S. David, J. R. Sampson, and J. P. Cheadle. 2002. Inherited variants of MYH associated with somatic G:C-> T:A mutations in colorectal tumors. Nat. Genet. 30:227-232.[CrossRef][Medline]
  2. Boiteux, S., and J. P. Radicella. 2000. The human OGG1 gene: structure, functions, and its implication in the process of carcinogenesis. Arch. Biochem. Biophys. 377:1-8.[CrossRef][Medline]
  3. Bolotin, A., P. Wincker, S. Mauge, O. Jaillon, K. Malarme, J. Weissenbach, S. D. Ehrlich, and A. Sorokin. 2001. The complete genome sequence of the lactic acid bacterium Lactococcus lactis ssp. lactis IL1403. Genome Res. 11:731-753.[Abstract/Free Full Text]
  4. Burkovski, A., and R. Krämer. 2002. Bacterial amino transport proteins: occurrence, functions, and significance for biotechnological applications. Appl. Microbiol. Biotechnol. 58:265-274.[CrossRef][Medline]
  5. Cabrera, M., Y. Nghiem, and J. H. Miller. 1988. mutM, a second mutator locus in Escherichia coli that generates GC->TA transversions. J. Bacteriol. 170:5405-5407.[Abstract/Free Full Text]
  6. Cupples, C. G., M. Cabrera, C. Cruz, and J. H. Miller. 1990. A set of lacZ mutations in Escherichia coli that allow rapid detection of specific frameshift mutations. Genetics 125:275-280.[Abstract]
  7. Dixon, W. J., and F. J. Massey, Jr. 1969. Introduction to statistical analysis. McGraw-Hill, New York, N.Y.
  8. Doiron, K. M., S. Viau, M. Koutroumanis, and C. G. Cupples. 1996. Overexpression of vsr in Escherichia coli is mutagenic. J. Bacteriol. 178:4294-4296.[Abstract/Free Full Text]
  9. Fishel, R. 2001. The selection for mismatch repair defects in hereditary nonpolyposis colorectal cancer: revising the mutator hypothesis. Cancer Res. 61:7369-7374.[Free Full Text]
  10. Fujikawa, N., H. Kurumizaka, O. Nureki, T. Terada, M. Shirouzu, T. Katayama, and S. Yokoyama. 2003. Structural basis of replication origin recognition by the DnaA protein. Nucleic Acids Res. 31:2077-2086.[Abstract/Free Full Text]
  11. Furuya, K., and C. R. Hutchinson. 1998. The DrrC protein of Streptomyces peucetius, a UvrA-like protein, is a DNA-binding protein whose gene is induced by daunorubicin. FEMS Microbiol. Lett. 168:243-249.[CrossRef][Medline]
  12. Garibyan, L., T. Huang, M. Kim, E. Wolff, A. Nguyen, T. Nguyen, A. Diep, K. Hu, A. Iverson, H. Yang, and J. H. Miller. 2003. Use of the rpoB gene to determine the specificity of base substitution mutations on the Escherichia coli chromosome. DNA Repair 2:593-608.[CrossRef][Medline]
  13. Glickman, B. W., and M. Radman. 1980. Escherichia coli mutator mutants deficient in methylation-instructed DNA mismatch correction. Proc. Natl. Acad. Sci. USA 77:1063-1067.[Abstract/Free Full Text]
  14. Goosen, N., and G. F. Moolenaar. 2001. Role of ATP hydrolysis by UvrA and UvrB during nucleotide excision repair. Res. Microbiol. 152:401-409.[Medline]
  15. Grigorian, A. V., R. B. Lustig, E. C. Guzman, J. M. Mahaffy, and J. W. Zyskind. 2003. Escherichia coli cells with increased levels of DnaA and deficient in recombinational repair have decreased viability. J. Bacteriol. 185:630-644.[Abstract/Free Full Text]
  16. Grkovic, S., M. H. Brown, and R. A. Skurray. 2002. Regulation of bacterial drug export systems. Microbiol. Mol. Biol. Rev. 66:671-701.[Abstract/Free Full Text]
  17. Heinen, C. D., C. Schmutte, and R. Fishel. 2002. DNA repair and tumorigenesis: lessons from hereditary cancer syndromes. Cancer Biol. Ther. 1:477-485.[Medline]
  18. Helling, R. B., B. K. Janes, H. Kimball, T. Tran, M. Bundesmann, P. Check, D. Phelan, and C. Miller. 2004. Toxic waste disposal in Escherichia coli. J. Bacteriol. 184:3699-3703.
  19. Hirai, K., S. Suzue, T. Irikura, S. Iyobe, and S. Mitsuhashi. 1987. Mutations producing resistance to norfloxacin in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 31:582-586.[Abstract/Free Full Text]
  20. Jones, S., P. Emmerson, J. Maynard, J. M. Best, S. Jordan, G. T. Williams, J. R. Sampson, and J. P. Cheadle. 2002. Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G:C-> T:A mutations. Hum. Mol. Genet. 11:2961-2967.[Abstract/Free Full Text]
  21. Kolodner, R. 1996. Biochemistry and genetics of eukaryotic mismatch repair. Genes Dev. 10:1433-1442.[Free Full Text]
  22. Loeb, L. A., K. R. Loeb, and J. P. Anderson. 2003. Multiple mutations and cancer. Proc. Natl. Acad. Sci. USA 100:776-781.[Abstract/Free Full Text]
  23. Lomovskaya, N., S. Hong, S. Kim, L. Fonstein, K. Furuya, and C. R. Hutchinson. 1996. The Streptomyces peucetius drrC gene encodes a UvrA-like protein involved in daunorubicin resistance and production. J. Bacteriol. 178:3238-3245.[Abstract/Free Full Text]
  24. Lomovskaya, O., and K. Lewis. 1992. emr, an Escherichia coli locus for multidrug resistance. Proc. Natl. Acad. Sci. USA 89:8938-8942.[Abstract/Free Full Text]
  25. Lomovskaya, O., K. Lewis, and A. Matin. 1995. EmrR is a negative regulator of the Escherichia coli multidrug resistance pump EmrAB. J. Bacteriol. 177:2328-2334.[Abstract/Free Full Text]
  26. Marinus, M. G., and N. R. Morris. 1975. Pleiotropic effects of a DNA adenine methylation mutation (dam-3) in Escherichia coli K12. Mutat. Res. 28:15-26.[CrossRef][Medline]
  27. Michaels, M. L., J. Tchou, A. P. Grollman, and J. H. Miller. 1992. A repair system for 8-oxo7,8-dihydrodeoxyguanine. Biochemistry 31:10964-10968.[CrossRef][Medline]
  28. Miller, J. H. 1992. A short course in bacterial genetics: a laboratory manual and handbook for Escherichia coli and related bacteria. Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.
  29. Miller, J. H. 1996. Spontaneous mutators in bacteria: insights into pathways of mutagenesis and repair. Annu. Rev. Microbiol. 50:625-643.[CrossRef][Medline]
  30. Miller, J. H. 1998. Mutators in Escherichia coli. Mutat. Res. 409:99-106.[Medline]
  31. Miller, J. H., P. Funchain, W. Clendenin, T. Huang, A. Nguyen, E. Wolff, A. Yeung, J. H. Chiang, L. Garibyan, M. M. Slupska, and H. Yang. 2002. Escherichia coli strains (ndk) lacking nucleoside diphosphate kinase are powerful mutators for base substitutions and frameshifts in mismatch repair-deficient strains. Genetics 162:5-13.[Abstract/Free Full Text]
  32. Modrich, P., and R. Lahue. 1996. Mismatch repair in replication fidelity, genetic recombination, and cancer biology. Annu. Rev. Biochem. 65:101-133.[CrossRef][Medline]
  33. Nakamura, H., Y. Oda, S. Iwai, H. Inoue, E. Ohtsuka, S. Kanaya, S. Kimura, C. Katsuda, K. Katayanagi, K. Morikawa, H. Miyashiro, and M. Ikehara. 1991. How does RNase H recognize a DNA-RNA hybrid? Proc. Natl. Acad. Sci. USA 88:11535-11539.[Abstract/Free Full Text]
  34. Nevers, P., and H. Spatz. 1975. Escherichia coli mutants uvrD uvrE deficient in gene conversion of lambda heteroduplexes. Mol. Gen. Genet. 139:233-243.[Medline]
  35. Nghiem, Y., M. Cabrera, C. G. Cupples, and J. H. Miller. 1988. The mutY gene: a mutator locus in Escherichia coli that generates G · C -> T · A transversions. Proc. Natl. Acad. Sci. USA 85:2709-2713.[Abstract/Free Full Text]
  36. Ohtani, N., M. Haruki, M. Morikawa, and S. Kanaya. 2001. Heat labile ribonuclease HI from a psychrotrophic bacterium: gene cloning, characterization and site directed mutagenesis. Protein Eng. 14:975-982.[Abstract/Free Full Text]
  37. Shiba, T., K. Ishiguro, N. Takemoto, H. Koibuchi, and K. Sugimoto. 1995. Purification and characterization of the Pseudomonas aeruginosa NfxB protein, the negative regulator or the nfxB gene. J. Bacteriol. 177:5872-5877.[Abstract/Free Full Text]
  38. Slupska, M. M., W. M. Luther, J. H. Chiang, H. Yang, and J. H. Miller. 1999. Functional expression of hMYH, a human homolog of the Escherichia coli MutY protein. J. Bacteriol. 181:6210-6213.[Abstract/Free Full Text]
  39. Stover, C. K., X. Q. Pham, A. L. Erwin, S. D. Mizoguchi, P. Warrener, M. J. Hickey, F. S. Brinkman, W. O. Hufnagle, D. J. Kowalik, M. Lagrou, R. L. Garber, L. Goltry, E. Tolentino, S. Westbrock-Wadman, Y. Yuan, L. L. Brody, S. N. Coulter, K. R. Folger, A. Kas, K. Larbig, R. Lim, K. Smith, D. Spencer, G. K. Wong, Z. Wu, I. T. Paulsen, J. Reizer, M. H. Saier, R. E. Hancock, S. Lory, and M. V. Olson. 2000. Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen. Nature 406:959-964.[CrossRef][Medline]
  40. Truong-Bolduc, Q. C., P. M. Dunman, J. Strahilevitz, S. J. Projan, and D. C. Hooper. 2005. MgrA is a multiple regulator of two new efflux pumps in Staphylococcus aureus. J. Bacteriol. 187:2395-2405.[Abstract/Free Full Text]
  41. Truong-Bolduc, Q. C., X. Zhang, and D. C. Cooper. 2003. Characterization of NorR protein, a multifunctional regulator of norA expression in Staphylococcus aureus. J. Bacteriol. 185:3127-3138.[Abstract/Free Full Text]
  42. Tucker, N. P., B. D'Autréaux, D. J. Studholme, S. Spiro, and R. Dixon. 2004. DNA binding activity of the Escherichia coli nitric oxide sensor NorR suggests a conserved target sequence in diverse proteobacteria. J. Bacteriol. 186:6656-6660.[Abstract/Free Full Text]
  43. Van Dyk, T. K., L. J. Templeton, K. A. Cantera, P. L. Sharpe, and F. S. Sariaslani. 2004. Characterization of the Escherichia coli AaeAB efflux pump: a metabolic relief valve? J. Bacteriol. 186:7196-7204.[Abstract/Free Full Text]
  44. Yang, H., W. M. Clendenin, D. Wong, B. Demple, M. M. Slupska, J. H. Chiang, and J. H. Miller. 2001. Enhanced activity of adenine-DNA glycosylase (Myh) by apurinic/apyrimidinic endonuclease (Ape1) in mammalian base excision repair of an A/GO mismatch. Nucleic Acids Res. 29:743-752.[Abstract/Free Full Text]
  45. Yang, H., E. Wolff, M. Kim, A. Diep, and J. H. Miller. 2004. Identification of mutator genes and mutation pathways in Escherichia coli using a multicopy cloning approach. Mol. Microbiol. 53:283-295.[CrossRef][Medline]

Journal of Bacteriology, July 2005, p. 5044-5048, Vol. 187, No. 14
0021-9193/05/$08.00+0     doi:10.1128/JB.187.14.5044-5048.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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