Abstract
The activated Ada protein triggers expression of DNA repair genes in Escherichia coli in response to alkylation damage. Ada also possesses two distinct suicide alkyltransferase activities, for O6-alkylguanines and for alkyl phosphotriesters in DNA. The mutant Ada3 and Ada5 transferases repair O6-methylguanine in DNA 20 and 3000 times more slowly, respectively, than the wild-type Ada protein, but both exhibit normal DNA phosphotriester repair. These same proteins also exhibit delayed and sluggish induction of the ada and alkA genes. Since the C-terminal O6-methylguanine methyltransferase domain of Ada is not implicated in the direct binding of specific DNA sequences, this part of the Ada protein is likely to play an alternative mechanistic role in gene activation, either by promoting Ada dimerization, or via direct contacts with RNA polymerase.
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- Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
- Cairns J. Efficiency of the adaptive response of Escherichia coli to alkylating agents. Nature. 1980 Jul 10;286(5769):176–178. doi: 10.1038/286176a0. [DOI] [PubMed] [Google Scholar]
- Demple B., Jacobsson A., Olsson M., Robins P., Lindahl T. Repair of alkylated DNA in Escherichia coli. Physical properties of O6-methylguanine-DNA methyltransferase. J Biol Chem. 1982 Nov 25;257(22):13776–13780. [PubMed] [Google Scholar]
- Demple B., Sedgwick B., Robins P., Totty N., Waterfield M. D., Lindahl T. Active site and complete sequence of the suicidal methyltransferase that counters alkylation mutagenesis. Proc Natl Acad Sci U S A. 1985 May;82(9):2688–2692. doi: 10.1073/pnas.82.9.2688. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Evensen G., Seeberg E. Adaptation to alkylation resistance involves the induction of a DNA glycosylase. Nature. 1982 Apr 22;296(5859):773–775. doi: 10.1038/296773a0. [DOI] [PubMed] [Google Scholar]
- Harris A. L., Karran P., Lindahl T. O6-Methylguanine-DNA methyltransferase of human lymphoid cells: structural and kinetic properties and absence in repair-deficient cells. Cancer Res. 1983 Jul;43(7):3247–3252. [PubMed] [Google Scholar]
- Hora J. F., Eastman A., Bresnick E. O6-methylguanine methyltransferase in rat liver. Biochemistry. 1983 Aug 2;22(16):3759–3763. doi: 10.1021/bi00285a007. [DOI] [PubMed] [Google Scholar]
- Jeggo P. Isolation and characterization of Escherichia coli K-12 mutants unable to induce the adaptive response to simple alkylating agents. J Bacteriol. 1979 Sep;139(3):783–791. doi: 10.1128/jb.139.3.783-791.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Karran P., Hjelmgren T., Lindahl T. Induction of a DNA glycosylase for N-methylated purines is part of the adaptive response to alkylating agents. Nature. 1982 Apr 22;296(5859):770–773. doi: 10.1038/296770a0. [DOI] [PubMed] [Google Scholar]
- Lemotte P. K., Walker G. C. Induction and autoregulation of ada, a positively acting element regulating the response of Escherichia coli K-12 to methylating agents. J Bacteriol. 1985 Mar;161(3):888–895. doi: 10.1128/jb.161.3.888-895.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lindahl T., Demple B., Robins P. Suicide inactivation of the E. coli O6-methylguanine-DNA methyltransferase. EMBO J. 1982;1(11):1359–1363. doi: 10.1002/j.1460-2075.1982.tb01323.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McCarthy J. G., Edington B. V., Schendel P. F. Inducible repair of phosphotriesters in Escherichia coli. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7380–7384. doi: 10.1073/pnas.80.24.7380. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McCarthy T. V., Karran P., Lindahl T. Inducible repair of O-alkylated DNA pyrimidines in Escherichia coli. EMBO J. 1984 Mar;3(3):545–550. doi: 10.1002/j.1460-2075.1984.tb01844.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McCarthy T. V., Lindahl T. Methyl phosphotriesters in alkylated DNA are repaired by the Ada regulatory protein of E. coli. Nucleic Acids Res. 1985 Apr 25;13(8):2683–2698. doi: 10.1093/nar/13.8.2683. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mitra S., Pal B. C., Foote R. S. O6-methylguanine-DNA methyltransferase in wild-type and ada mutants of Escherichia coli. J Bacteriol. 1982 Oct;152(1):534–537. doi: 10.1128/jb.152.1.534-537.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nakabeppu Y., Kondo H., Kawabata S., Iwanaga S., Sekiguchi M. Purification and structure of the intact Ada regulatory protein of Escherichia coli K12, O6-methylguanine-DNA methyltransferase. J Biol Chem. 1985 Jun 25;260(12):7281–7288. [PubMed] [Google Scholar]
- Nakabeppu Y., Mine Y., Sekiguchi M. Regulation of expression of the cloned ada gene in Escherichia coli. Mutat Res. 1985 Sep;146(2):155–167. doi: 10.1016/0167-8817(85)90006-9. [DOI] [PubMed] [Google Scholar]
- Olsson M., Lindahl T. Repair of alkylated DNA in Escherichia coli. Methyl group transfer from O6-methylguanine to a protein cysteine residue. J Biol Chem. 1980 Nov 25;255(22):10569–10571. [PubMed] [Google Scholar]
- Pegg A. E., Wiest L., Foote R. S., Mitra S., Perry W. Purification and properties of O6-methylguanine-DNA transmethylase from rat liver. J Biol Chem. 1983 Feb 25;258(4):2327–2333. [PubMed] [Google Scholar]
- Robins P., Cairns J. Quantitation of the adaptive response to alkylating agents. Nature. 1979 Jul 5;280(5717):74–76. doi: 10.1038/280074a0. [DOI] [PubMed] [Google Scholar]
- Robins P., Harris A. L., Goldsmith I., Lindahl T. Cross-linking of DNA induced by chloroethylnitrosourea is presented by O6-methylguanine-DNA methyltransferase. Nucleic Acids Res. 1983 Nov 25;11(22):7743–7758. doi: 10.1093/nar/11.22.7743. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Samson L., Cairns J. A new pathway for DNA repair in Escherichia coli. Nature. 1977 May 19;267(5608):281–283. doi: 10.1038/267281a0. [DOI] [PubMed] [Google Scholar]
- Sedgwick B. Molecular cloning of a gene which regulates the adaptive response to alkylating agents in Escherichia coli. Mol Gen Genet. 1983;191(3):466–472. doi: 10.1007/BF00425764. [DOI] [PubMed] [Google Scholar]
- Teo I., Sedgwick B., Demple B., Li B., Lindahl T. 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. EMBO J. 1984 Sep;3(9):2151–2157. doi: 10.1002/j.1460-2075.1984.tb02105.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Teo I., Sedgwick B., Kilpatrick M. W., McCarthy T. V., Lindahl T. The intracellular signal for induction of resistance to alkylating agents in E. coli. Cell. 1986 Apr 25;45(2):315–324. doi: 10.1016/0092-8674(86)90396-x. [DOI] [PubMed] [Google Scholar]
- Volkert M. R., Nguyen D. C., Beard K. C. Escherichia coli gene induction by alkylation treatment. Genetics. 1986 Jan;112(1):11–26. doi: 10.1093/genetics/112.1.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Volkert M. R., Nguyen D. C. Induction of specific Escherichia coli genes by sublethal treatments with alkylating agents. Proc Natl Acad Sci U S A. 1984 Jul;81(13):4110–4114. doi: 10.1073/pnas.81.13.4110. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wickner W., Schekman R., Geider K., Kornberg A. A new form of DNA polymerase 3 and a copolymerase replicate a long, single-stranded primer-template. Proc Natl Acad Sci U S A. 1973 Jun;70(6):1764–1767. doi: 10.1073/pnas.70.6.1764. [DOI] [PMC free article] [PubMed] [Google Scholar]