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Gene Review

ada  -  fused DNA-binding transcriptional dual...

Escherichia coli str. K-12 substr. MG1655

Synonyms: ECK2205, JW2201
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Disease relevance of ada


High impact information on ada


Chemical compound and disease context of ada


Biological context of ada


Anatomical context of ada

  • Plasmids containing an N-terminal fragment of the ada+ gene which encoded only one of the two methyltransferase activities of the Ada protein did not significantly protect E. coli or CHO cells against MNNG [18].
  • However, NIH-3T3 cells expressing ada were only slightly more resistant to BCNU than controls, possibly because most of the ada protein was cytoplasmic rather than nuclear as suggested by immunohistochemical stain [3].
  • O6-alkylguanine-DNA-alkyltransferase (ATase)-deficient murine haemopoietic stem cells were transfected, following electroporation, with a G418-selectable expression vector containing the protein coding region of the Escherichia coli ATase gene ada [19].
  • After recombination with a Chinese hamster metallothionein I gene promoter, the ada gene was microinjected into C3H/HeN mouse zygotes [20].

Associations of ada with chemical compounds

  • However, responses of the two transcription reactions to methylating agents differed; ada transcription was stimulated by methylnitrosourea, while alkA transcription was suppressed [21].
  • Genes belonging to the adaptive response are positively regulated by the ada gene; the Ada protein acts as a transcriptional activator when methylated in one of its cysteine residues at position 69 [22].
  • We constructed hybrid plasmids carrying an alkB'-lacZ' fusion, with or without the ada control region, and investigated expression of the alkB gene in response to the alkylating agent [17].
  • Transfer of a methyl group to Cys-69 by repair of a methylphosphotriester lesion converts Ada into a transcriptional activator of the ada and alkA genes [9].
  • AdaK178P (lysine 178 changed to proline) is completely defective for the transcriptional activation function of ada while it is completely proficient for transcriptional activation of alkA [9].

Regulatory relationships of ada

  • Deletion of the carboxyl-terminal 67 amino acids of Ada abolished the ability of the unmethylated form of the protein to inhibit activation of ada transcription but not the ability of the methylated form to activate ada or alkA transcription [23].
  • Although ogt was expressed at slightly higher levels than the truncated ada in the transfected cells, this could not account for the differential protection observed [24].
  • Expression of the Escherichia coli aidB gene is induced in vivo by alkylation damage in an ada-dependent pathway and by anaerobiosis or by acetate at pH 6.5 in an ada-independent fashion [25].

Other interactions of ada

  • Common features in the Ada-binding regions of ada and aidB are a high A/T content, the presence of an inverted repeat structure, and their position relative to the transcriptional start site [22].
  • Furthermore, an increase in the level of the Ada protein, caused by the runaway plasmid pYN3059 in which the ada gene is regulated by the lac promoter, inhibited UV-mediated recA gene expression even in cells to which the MNNG-adaptive treatment had not been applied [26].
  • A recA-ada hybrid gene inducible by DNA damage [27].

Analytical, diagnostic and therapeutic context of ada


  1. Purification and structure of the intact Ada regulatory protein of Escherichia coli K12, O6-methylguanine-DNA methyltransferase. Nakabeppu, Y., Kondo, H., Kawabata, S., Iwanaga, S., Sekiguchi, M. J. Biol. Chem. (1985) [Pubmed]
  2. Bacillus subtilis alkA gene encoding inducible 3-methyladenine DNA glycosylase is adjacent to the ada operon. Morohoshi, F., Hayashi, K., Munkata, N. J. Bacteriol. (1993) [Pubmed]
  3. Increase in nitrosourea resistance in mammalian cells by retrovirally mediated gene transfer of bacterial O6-alkylguanine-DNA alkyltransferase. Dumenco, L.L., Warman, B., Hatzoglou, M., Lim, I.K., Abboud, S.L., Gerson, S.L. Cancer Res. (1989) [Pubmed]
  4. Expression of the truncated E. coli O6-methylguanine methyltransferase gene in repair-deficient human cells and restoration of cellular resistance to alkylating agents. Ishizaki, K., Tsujimura, T., Fujio, C., Zhang, Y.P., Yawata, H., Nakabeppu, Y., Sekiguchi, M., Ikenaga, M. Mutat. Res. (1987) [Pubmed]
  5. The intracellular signal for induction of resistance to alkylating agents in E. coli. Teo, I., Sedgwick, B., Kilpatrick, M.W., McCarthy, T.V., Lindahl, T. Cell (1986) [Pubmed]
  6. A methylation-dependent electrostatic switch controls DNA repair and transcriptional activation by E. coli ada. He, C., Hus, J.C., Sun, L.J., Zhou, P., Norman, D.P., Dötsch, V., Wei, H., Gross, J.D., Lane, W.S., Wagner, G., Verdine, G.L. Mol. Cell (2005) [Pubmed]
  7. Cloning and expression in Escherichia coli of a gene for an alkylbase DNA glycosylase from Saccharomyces cerevisiae; a homologue to the bacterial alkA gene. Berdal, K.G., Bjørås, M., Bjelland, S., Seeberg, E. EMBO J. (1990) [Pubmed]
  8. Kinetic studies of the modulation of ada promoter activity by upstream elements. Bertrand-Burggraf, E., Dunand, J., Fuchs, R.P., Lefèvre, J.F. EMBO J. (1990) [Pubmed]
  9. Alteration of lysine 178 in the hinge region of the Escherichia coli ada protein interferes with activation of ada, but not alkA, transcription. Saget, B.M., Shevell, D.E., Walker, G.C. J. Bacteriol. (1995) [Pubmed]
  10. A single amino acid change in human O6-alkylguanine-DNA alkyltransferase decreasing sensitivity to inactivation by O6-benzylguanine. Crone, T.M., Pegg, A.E. Cancer Res. (1993) [Pubmed]
  11. Functional sites of the Ada regulatory protein of Escherichia coli. Analysis by amino acid substitutions. Takano, K., Nakabeppu, Y., Sekiguchi, M. J. Mol. Biol. (1988) [Pubmed]
  12. Construction and characterization of mutants of Salmonella typhimurium deficient in DNA repair of O6-methylguanine. Yamada, M., Sedgwick, B., Sofuni, T., Nohmi, T. J. Bacteriol. (1995) [Pubmed]
  13. Inhibitory effect of cadmium and mercury ions on induction of the adaptive response in Escherichia coli. Takahashi, K., Imaeda, T., Kawazoe, Y. Mutat. Res. (1991) [Pubmed]
  14. Induction and autoregulation of ada, a positively acting element regulating the response of Escherichia coli K-12 to methylating agents. Lemotte, P.K., Walker, G.C. J. Bacteriol. (1985) [Pubmed]
  15. Mutagenesis and DNA repair for alkylation damages in Escherichia coli K-12. Abril, N., Roldán-Arjona, T., Prieto-Alamo, M.J., van Zeeland, A.A., Pueyo, C. Environ. Mol. Mutagen. (1992) [Pubmed]
  16. Induction of resistance to alkylating agents in E. coli: the ada+ gene product serves both as a regulatory protein and as an enzyme for repair of mutagenic damage. Teo, I., Sedgwick, B., Demple, B., Li, B., Lindahl, T. EMBO J. (1984) [Pubmed]
  17. Structure and expression of the alkB gene of Escherichia coli related to the repair of alkylated DNA. Kondo, H., Nakabeppu, Y., Kataoka, H., Kuhara, S., Kawabata, S., Sekiguchi, M. J. Biol. Chem. (1986) [Pubmed]
  18. Complementation of sensitivity to alkylating agents in Escherichia coli and Chinese hamster ovary cells by expression of a cloned bacterial DNA repair gene. Kataoka, H., Hall, J., Karran, P. EMBO J. (1986) [Pubmed]
  19. Transfection of murine multi-potent haemopoietic stem cells with an E. coli DNA alkyltransferase gene confers resistance to the toxic effects of alkylating agents. Jelinek, J., Kleibl, K., Dexter, T.M., Margison, G.P. Carcinogenesis (1988) [Pubmed]
  20. Enhanced O6-methylguanine-DNA methyltransferase activity in transgenic mice containing an integrated E. coli ada repair gene. Matsukuma, S., Nakatsuru, Y., Nakagawa, K., Utakoji, T., Sugano, H., Kataoka, H., Sekiguchi, M., Ishikawa, T. Mutat. Res. (1989) [Pubmed]
  21. Regulatory mechanisms for induction of synthesis of repair enzymes in response to alkylating agents: ada protein acts as a transcriptional regulator. Nakabeppu, Y., Sekiguchi, M. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  22. Transcriptional activation of the Escherichia coli adaptive response gene aidB is mediated by binding of methylated Ada protein. Evidence for a new consensus sequence for Ada-binding sites. Landini, P., Volkert, M.R. J. Biol. Chem. (1995) [Pubmed]
  23. The Ada protein acts as both a positive and a negative modulator of Escherichia coli's response to methylating agents. Saget, B.M., Walker, G.C. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  24. Expression in mammalian cells of the Escherichia coli O6 alkylguanine-DNA-alkyltransferase gene ogt reduces the toxicity of alkylnitrosoureas. Harris, L.C., Margison, G.P. Br. J. Cancer (1993) [Pubmed]
  25. Structure and transcriptional regulation of the Escherichia coli adaptive response gene aidB. Landini, P., Hajec, L.I., Volkert, M.R. J. Bacteriol. (1994) [Pubmed]
  26. Inhibition of the SOS response of Escherichia coli by the Ada protein. Vericat, J.A., Guerrero, R., Barbé, J. J. Bacteriol. (1988) [Pubmed]
  27. A recA-ada hybrid gene inducible by DNA damage. Kleibl, K., Margison, G.P., Skorvaga, M., Brozmanová, J., Masek, F. Mutat. Res. (1992) [Pubmed]
  28. The adaptive response to alkylation damage. Constitutive expression through a mutation in the coding region of the ada gene. Hughes, S.J., Sedgwick, B. J. Biol. Chem. (1989) [Pubmed]
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