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Gene Review

lacI  -  lactose-inducible lac operon...

Escherichia coli str. K-12 substr. MG1655

Synonyms: ECK0342, JW0336
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Disease relevance of lacI

  • Cell killing and mutation induction by cis- and trans-Pt(NH3)2Cl2 in Escherichia coli were examined by studying forward mutagenesis in the lacI gene in cells with different repair capacities [1].
  • Recovery of lacI- genes from F is based on the conversion of this lacI+Z- alpha phage to lacI-Z+ alpha by recombination with F'lacI-Z+ [2].
  • The chromosomal DNA that lies between the lacI and lacZ genes of Klebsiella pneumoniae constitutes a 196-base pair intercistronic region that contains regulatory sequences for both genes [3].
  • High-level, inducible expression of heterologous genes in the cyanobacterium Synechococcus sp. strain PCC 7942 was obtained using the Escherichia coli trc promoter and lacI repressor [4].
  • We have investigated the use of various Epstein-Barr virus (EBV)-based vectors bearing the two components of the Escherichia coli lac operator-repressor (lacO, lacI) complex [5].

High impact information on lacI

  • DNA recognition by lac repressor and catabolite activator protein is greatly stimulated, while specific aroH DNA recognition by trp repressor is inhibited [6].
  • Thus lac repressor-operator complexes can form on primate chromosomes and stringently block transcription from an adjoining promoter [7].
  • Monkey cell lines that constitutively synthesize 38.6 kd lac repressor protein and bear stably integrated chloramphenicol acetyl transferase (CAT) genes linked to a lac operator-containing SV40 early promoter-enhancer were generated [7].
  • Stringent regulation of stably integrated chloramphenicol acetyl transferase genes by E. coli lac repressor in monkey cells [7].
  • Repression of large T synthesis or CAT activity occurred in vivo only when the respective operator-containing plasmid was cotransfected with a plasmid encoding lac repressor, or when the recipient cells stably synthesized lac repressor [8].

Chemical compound and disease context of lacI


Biological context of lacI

  • Transcription of the Escherichia coli lac repressor gene (lacI) in vivo produces monocistronic mRNAs with discrete 3' ends in the lac control region, although the DNA sequence of this region does not specify a strong termination signal of the traditional form [14].
  • Doxorubicin-induced single base substitutions were highly focused at one site (4 of 6) in the i-d region of lacI, in contrast to the spontaneous distribution of point mutations, where 16 mutants were recovered at 12 different sites [9].
  • The sequencing of over 6000 lacI- mutations has revealed 193 missense mutations generating 189 amino acid replacements at 102 different sites within the lac repressor [15].
  • There is also 25% identity between the amino acid sequence of lacI and the deduced amino acid sequence of ebgR [16].
  • In addition to this effect on transversions within the lacI gene, one previously recognized A.T-->G.C base-pair substitution hotspot in the lac operator is also reduced (approximately 5-fold) [17].

Anatomical context of lacI


Associations of lacI with chemical compounds

  • The 5'-endpoints of doxorubicin-induced lacO and lacI/lacO deletions occurred at the DNA sequence 5'-pyTAA or 5'-AATpy (where py is pyrmidine) (16%), at runs of purines or pyrimidines (41%) and adjacent to 5'-dGdC or 5'-dCdG doublets (34%) [9].
  • To broaden our knowledge about the mutagenic specificity of SOS-dependent mutagens, we determined the mutational specificity of 233 suppressible lacI mutations induced by angelicin [11].
  • However, characterization of lacI nonsense mutations induced by thymine starvation demonstrated that G:C----A:T transitions and all four possible transversions also occurred [23].
  • Subsequent introduction of the lacI gene into IIB1 cells resulted in correct transcriptional repression of the lacZ gene that could be alleviated by IPTG, an allosteric inducer of lacI repression [24].
  • (3) There was no observable preference for particular sequences of furazolidone-induced mutations; the prominent hotspots for AF2-induced G:C-->T:A transversions, G:C-->A:T transitions and -(G:C) frameshifts were at 5'-TGC-3' sequences in the lacI gene [25].

Regulatory relationships of lacI

  • The heavy chain and the light chain-gIII fusion are transcribed as a polycistronic mRNA from the lacZ promoter and efficient transcriptional control is provided by wildtype lacI present on the vector [26].

Other interactions of lacI

  • Analysis of reverse mutations in lacZ and forward nonsense mutations in lacI showed that the mutA strain has higher levels of A.T----T.A and G.C----T.A transversions, and to a lesser degree A.T----C.G transversions [27].
  • To investigate the specificity of these antimutator effects, we have analyzed spectra of forward mutations in the N-terminal part of the lacI gene (i-d mutations) for two of the mutL dnaE derivatives (dnaE911 and dnaE915), as well as the control mutL strain [28].
  • Searches of the Y. pestis genome databases revealed the presence of noncontiguous sequences highly homologous to Escherichia coli lacZ, lacY, and lacI [29].
  • Strain MM6-13 (ptsI suc lacI sup) of Escherichia coli contains a suppressor of the succinate-negative phenotype [30].
  • The lac repressor from the lacI gene and the chimeric protein from a hupB' ::lac'Z fusion gene, whose start codons are GUG, were also synthesised in the deletion mutant [31].

Analytical, diagnostic and therapeutic context of lacI


  1. Base-pair substitution hotspots in GAG and GCG nucleotide sequences in Escherichia coli K-12 induced by cis-diamminedichloroplatinum (II). Brouwer, J., van de Putte, P., Fichtinger-Schepman, A.M., Reedijk, J. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  2. Rapid repeated cloning of mutant lac repressor genes. Schaaper, R.M., Danforth, B.N., Glickman, B.W. Gene (1985) [Pubmed]
  3. Regulatory region of the divergent Klebsiella pneumoniae lac operon. Buvinger, W.E., Riley, M. J. Bacteriol. (1985) [Pubmed]
  4. Inducible expression of heterologous genes targeted to a chromosomal platform in the cyanobacterium Synechococcus sp. PCC 7942. Geerts, D., Bovy, A., de Vrieze, G., Borrias, M., Weisbeek, P. Microbiology (Reading, Engl.) (1995) [Pubmed]
  5. Regulation of the Escherichia coli lac operon expressed in human cells. Biard, D.S., James, M.R., Cordier, A., Sarasin, A. Biochim. Biophys. Acta (1992) [Pubmed]
  6. DNA dynamic flexibility and protein recognition: differential stimulation by bacterial histone-like protein HU. Flashner, Y., Gralla, J.D. Cell (1988) [Pubmed]
  7. Stringent regulation of stably integrated chloramphenicol acetyl transferase genes by E. coli lac repressor in monkey cells. Figge, J., Wright, C., Collins, C.J., Roberts, T.M., Livingston, D.M. Cell (1988) [Pubmed]
  8. lac repressor can regulate expression from a hybrid SV40 early promoter containing a lac operator in animal cells. Brown, M., Figge, J., Hansen, U., Wright, C., Jeang, K.T., Khoury, G., Livingston, D.M., Roberts, T.M. Cell (1987) [Pubmed]
  9. DNA sequence specificity of doxorubicin-induced mutational damage in uvrB- Escherichia coli. Anderson, R.D., Veigl, M.L., Baxter, J., Sedwick, W.D. Cancer Res. (1991) [Pubmed]
  10. Lac repressor mRNA transcription terminates in vivo in the lac control region. Cone, K.C., Sellitti, M.A., Steege, D.A. J. Biol. Chem. (1983) [Pubmed]
  11. Suppressible base substitution mutations induced by angelicin (isopsoralen) in the Escherichia coli lacI gene: implications for the mechanism of SOS mutagenesis. Miller, S.S., Eisenstadt, E. J. Bacteriol. (1987) [Pubmed]
  12. Effect of deficiency in excision repair and umuC function on the mutagenicity with ethylene oxide in the lacI gene of E. coli. Kolman, A. Mutat. Res. (1985) [Pubmed]
  13. Sites of preferential induction of cyclobutane pyrimidine dimers in the nontranscribed strand of lacI correspond with sites of UV-induced mutation in Escherichia coli. Koehler, D.R., Awadallah, S.S., Glickman, B.W. J. Biol. Chem. (1991) [Pubmed]
  14. lac repressor blocks in vivo transcription of lac control region DNA. Sellitti, M.A., Pavco, P.A., Steege, D.A. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  15. Missense mutation in the lacI gene of Escherichia coli. Inferences on the structure of the repressor protein. Gordon, A.J., Burns, P.A., Fix, D.F., Yatagai, F., Allen, F.L., Horsfall, M.J., Halliday, J.A., Gray, J., Bernelot-Moens, C., Glickman, B.W. J. Mol. Biol. (1988) [Pubmed]
  16. Sequence of the ebgR gene of Escherichia coli: evidence that the EBG and LAC operons are descended from a common ancestor. Stokes, H.W., Hall, B.G. Mol. Biol. Evol. (1985) [Pubmed]
  17. Spontaneous mutation in Escherichia coli containing the dnaE911 DNA polymerase antimutator allele. Oller, A.R., Schaaper, R.M. Genetics (1994) [Pubmed]
  18. Activity of Lac repressor anchored to the Escherichia coli inner membrane. Görke, B., Reinhardt, J., Rak, B. Nucleic Acids Res. (2005) [Pubmed]
  19. Control of gene expression in tobacco cells using a bacterial operator-repressor system. Wilde, R.J., Shufflebottom, D., Cooke, S., Jasinska, I., Merryweather, A., Beri, R., Brammar, W.J., Bevan, M., Schuch, W. EMBO J. (1992) [Pubmed]
  20. The lacI shuttle: rapid analysis of the mutagenic specificity of ultraviolet light in human cells. Lebkowski, J.S., Clancy, S., Miller, J.H., Calos, M.P. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  21. Transposition of an Alu-containing element induced by DNA-advanced glycosylation endproducts. Bucala, R., Lee, A.T., Rourke, L., Cerami, A. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  22. Modifications of the E.coli Lac repressor for expression in eukaryotic cells: effects of nuclear signal sequences on protein activity and nuclear accumulation. Fieck, A., Wyborski, D.L., Short, J.M. Nucleic Acids Res. (1992) [Pubmed]
  23. Mechanism of mutation by thymine starvation in Escherichia coli: clues from mutagenic specificity. Kunz, B.A., Glickman, B.W. J. Bacteriol. (1985) [Pubmed]
  24. The design of a new mutation model for active genes: expression of the Escherichia coli lac operon in mammalian cells. van Sloun, P.P., Lohman, P.H., Vrieling, H. Mutat. Res. (1997) [Pubmed]
  25. The mutational specificity of furazolidone in the lacI gene of Escherichia coli. Bertenyi, K.K., Lambert, I.B. Mutat. Res. (1996) [Pubmed]
  26. Efficient method for constructing comprehensive murine Fab antibody libraries displayed on phage. Orum, H., Andersen, P.S., Oster, A., Johansen, L.K., Riise, E., Bjørnvad, M., Svendsen, I., Engberg, J. Nucleic Acids Res. (1993) [Pubmed]
  27. mutA and mutC: two mutator loci in Escherichia coli that stimulate transversions. Michaels, M.L., Cruz, C., Miller, J.H. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  28. The mutational specificity of two Escherichia coli dnaE antimutator alleles as determined from lacI mutation spectra. Schaaper, R.M. Genetics (1993) [Pubmed]
  29. Yersinia pestis lacZ expresses a beta-galactosidase with low enzymatic activity. Bobrov, A.G., Perry, R.D. FEMS Microbiol. Lett. (2006) [Pubmed]
  30. Suppression of defects in cyclic adenosine 3',5'-monophosphate metabolism in Escherichia coli. Alexander, J.K. J. Bacteriol. (1980) [Pubmed]
  31. Construction and characterization of an Escherichia coli mutant with a deletion of the metZ gene encoding tRNA (f1Met). Kenri, T., Kohno, K., Goshima, N., Imamoto, F., Kano, Y. Gene (1991) [Pubmed]
  32. Expression of a ciliate gene in Escherichia coli using a suppressor tRNA to read the UAA and UAG glutamine codons. Cohen, J., Dupuis, P., Viguès, B. J. Mol. Biol. (1990) [Pubmed]
  33. lac repressor: crystallization of intact tetramer and its complexes with inducer and operator DNA. Pace, H.C., Lu, P., Lewis, M. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  34. Amino-acid sequence of lac repressor from Escherichia coli. Isolation, sequence analysis and sequence assembly of tryptic peptides and cyanogen-bromide fragments. Beyreuther, K., Adler, K., Fanning, E., Murray, C., Klemm, A., Geisler, N. Eur. J. Biochem. (1975) [Pubmed]
  35. Induction of specific frameshift and base substitution events by benzo[a]pyrene diol epoxide in excision-repair-deficient Escherichia coli. Bernelot-Moens, C., Glickman, B.W., Gordon, A.J. Carcinogenesis (1990) [Pubmed]
  36. A new technique for determining the distribution of N7-methylguanine using an automated DNA sequencer. Shoukry, S., Anderson, M.W., Glickman, B.W. Carcinogenesis (1991) [Pubmed]
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