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Escherichia coli K-12 substr. MG1655 Enzyme: AlkB repair system for alkylated DNA and RNA



Gene: alkB Accession Numbers: EG10037 (EcoCyc), b2212, ECK2204

Synonyms: aidD

Regulation Summary Diagram: ?

Summary:
AlkB is a Fe(II)-containing, 2-oxoglutarate-dependent dioxygenase involved in the adaptive DNA-repair response of E. coli to alkylating agents. AlkB catalyzes repair of DNA lesions caused by SN2 alkylating compounds which affect N1 of purines and N3 of pyrimidines, in contrast to lesions caused by SN1 alkylating compounds or ionizing radiation [Dinglay00]. AlkB preferentially binds to and repairs alkylation lesions in single-stranded DNA over double-stranded DNA, suggesting that AlkB repair activity may be specific for the single-stranded DNA present during transcription and DNA replication (when base excision repair would not work) [Dinglay00, Falnes04, Yi09]. AlkB also catalyzes repair of alkylated RNA [Aas03, Ougland04, Vagbo12]. AlkB is unable to repair single, alkylated nucleosides or bases as efficiently as oligomers [Welford03] unless they are 5'-phosphorylated [Koivisto03].

Overproduction and purification of the protein is described leading to analysis of substrate binding and enzyme assays [Kondo86, Mishina04, Sedgwick06]. alkB mutants are susceptible to the toxicity and mutagenicity of alkylation lesions [Delaney04, Sedgwick06]. Mutation analysis shows AlkB is also responsible for eliminating exocylic base adducts induced by 2-chloroacetaldehyde [Kim07g]. An alkB mutant exhibits increased sensitivity to methyl methanesulfonate (MMS) and a defect in repair of MMS-treated phage, compared to wild type, but shows wild-type sensitivity to UV irradiation and a wild-type response to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) [Kataoka83, Nieminuszczy06]. The BS23 mutation results in deletion of the ada-alkB operon [Rebeck88]. The aidD6::Mu d1 (bla lac) mutation disrupts the alkB gene [Volkert91]. An alkB mutant does not exhibit defects in repair of apyrimidinic and apurinic DNA site lesions or crosslinks that occur at such lesions [Dinglay98]. An alkB mutant does not exhibit sensitivity to the DNA minor groove alkylating agent MeOSO2-(CH2)2-Lex [Dinglay98]. Mutation of alkB does not affect enhancement by o-vanillin of MNNG mutagenesis in E. coli B [Watanabe90] nor does it affect the UVM (UV modulation of mutagenesis) effect [Wang95d].

Crystal structures of substrate and product complexes of AlkB have been determined [Yu06c, Yu09b] and nuclear magnetic resonance spectroscopy shows that these complexes have significantly different dynamic properties in solution [Bleijlevens08]. The Fe(II) cofactor of AlkB has been replaced with Cu(II) in a study probing the active site of the enzyme [Bleijlevens07]. AlkB-dsDNA complexes containing 3-methyl cytosine, 3-methyl thymine or a cyclic adduct have been crystallised and the structures resolved to high resolution [Yi10a].

Regulation has been described [Kondo86, Vasileva99]. Gene expression is activated by self-methylation of the Ada protein upon interaction with alkylated DNA [Teo86]. Gene expression is induced by the alkylating agents MMS [Volkert86], MNNG [Volkert86, Fram88], streptozotocin (STZ), and N-methyl-N-nitrosourea (MNU) [Fram88]. Methylation is a more effective inducer than some other types of alkylation [Volkert89]. Gene expression is not induced by heat shock [Fabisiewicz92], pH changes, thiosalicyclic acid, or N-ethylmaleimide treatment [Smirnova94].

AlkB has 23% identity to human ABH protein [Wei96a] and similarity to human ABH2 and ABH3 [Duncan02]. AlkB has 42% identity to Caulobacter crescentus AlkB [Colombi97]. AlkB is a member of the iron-dependent, 2-oxoglutarate-dependent dioxygenase protein family [Trewick02, Falnes02]. Expression of ada and alkB genes in human cells increases the cellular resistance to alkylation [Samson86]. Expression of alkB alone in human cells increases resistance specifically to SN2 alkylation compounds but not to SN1 alkylation compounds, the same spectrum of resistance that AlkB provides in E. coli [Chen94e]. Expression of the Saccharomyces cerevisiae YFW1, YFW12, or YFW16 gene functionally complements the MMS resistance of an E. coli alkB mutant [Wei95].

Reviews: [Volkert88, Sedgwick02, Jiricny02, Margison02, Begley03, Begley03a, Falnes03, Sedgwick04, Drablos04, Falnes05, Janion06, Mishina06, Falnes07].

AidD: "alkylation-inducible" [Volkert86].

Citations: [Nieminuszczy06a, Shivarattan05, Welford05, Henshaw04, Mishina04a, Mishina03]

Locations: cytosol

Map Position: [2,306,713 <- 2,307,363] (49.72 centisomes)
Length: 651 bp / 216 aa

Molecular Weight of Polypeptide: 24.076 kD (from nucleotide sequence), 27 kD (experimental) [Kataoka85 ]

Unification Links: ASAP:ABE-0007308 , CGSC:18544 , DIP:DIP-9085N , EchoBASE:EB0036 , EcoGene:EG10037 , EcoliWiki:b2212 , Mint:MINT-1258339 , OU-Microarray:b2212 , PDB:3O1M , PDB:3O1O , PDB:3O1P , PDB:3O1R , PDB:3O1S , PDB:3O1T , PDB:3O1U , PDB:3O1V , PortEco:alkB , PR:PRO_000022078 , Protein Model Portal:P05050 , RefSeq:NP_416716 , RegulonDB:EG10037 , SMR:P05050 , String:511145.b2212 , Swiss-Model:P05050 , UniProt:P05050

Relationship Links: InterPro:IN-FAMILY:IPR004574 , InterPro:IN-FAMILY:IPR005123 , InterPro:IN-FAMILY:IPR027450 , PDB:Structure:2FD8 , PDB:Structure:2FDF , PDB:Structure:2FDG , PDB:Structure:2FDH , PDB:Structure:2FDI , PDB:Structure:2FDJ , PDB:Structure:2FDK , PDB:Structure:3BI3 , PDB:Structure:3BIE , PDB:Structure:3BKZ , PDB:Structure:3I2O , PDB:Structure:3I3M , PDB:Structure:3I3Q , PDB:Structure:3I49 , PDB:Structure:3KHB , PDB:Structure:3KHC , PDB:Structure:3T3Y , PDB:Structure:3T4H , PDB:Structure:3T4V , PDB:Structure:4JHT , Pfam:IN-FAMILY:PF13532 , Prosite:IN-FAMILY:PS51471

Gene-Reaction Schematic: ?

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0006281 - DNA repair Inferred from experiment Inferred by computational analysis [UniProtGOA11a, GOA01a, Kataoka83]
GO:0006307 - DNA dealkylation involved in DNA repair Inferred from experiment [Yu06c, Aas03, Trewick02]
GO:0035552 - oxidative single-stranded DNA demethylation Inferred from experiment [Aas03]
GO:0035553 - oxidative single-stranded RNA demethylation Inferred from experiment [Aas03]
GO:0042245 - RNA repair Inferred from experiment [Aas03]
GO:0070989 - oxidative demethylation Inferred from experiment [Yu06c, Falnes02]
GO:0080111 - DNA demethylation Inferred from experiment [Yu06c]
GO:0006974 - cellular response to DNA damage stimulus Inferred by computational analysis [UniProtGOA11a]
GO:0055114 - oxidation-reduction process Inferred by computational analysis [UniProtGOA11a, GOA01a]
Molecular Function: GO:0008198 - ferrous iron binding Inferred from experiment [Yu06c, Trewick02]
GO:0035515 - oxidative RNA demethylase activity Inferred from experiment [Aas03]
GO:0043734 - DNA-N1-methyladenine dioxygenase activity Inferred from experiment [Yi10a, Yu06c, Aas03]
GO:0051213 - dioxygenase activity Inferred from experiment Inferred by computational analysis [UniProtGOA11a, Trewick02]
GO:0051747 - cytosine C-5 DNA demethylase activity Inferred from experiment [Yu06c]
GO:0016491 - oxidoreductase activity Inferred by computational analysis [UniProtGOA11a]
GO:0016706 - oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors Inferred by computational analysis [GOA01a]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005737 - cytoplasm
GO:0005829 - cytosol

MultiFun Terms: information transfer DNA related DNA repair

Essentiality data for alkB knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]

Credits:
Last-Curated ? 12-May-2008 by Johnson A , JCVI


Enzymatic reaction of: DNA oxidative demethylase (AlkB repair system for alkylated DNA and RNA)

EC Number: 1.14.11.33

a methylated nucleobase within DNA + 2-oxoglutarate + oxygen <=> a nucleobase within DNA + CO2 + formaldehyde + succinate + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown.


Enzymatic reaction of: 1-ethyladenine demethylase (AlkB repair system for alkylated DNA and RNA)

EC Number: 1.14.11.33

1-ethyladenine + 2-oxoglutarate + oxygen <=> adenine + CO2 + acetaldehyde + succinate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown.

Cofactors or Prosthetic Groups: Fe2+ [Duncan02]


Enzymatic reaction of: N3-methylcytosine demethylase (AlkB repair system for alkylated DNA and RNA)

EC Number: 1.14.11.33

N3-methylcytosine + 2-oxoglutarate + oxygen <=> cytosine + CO2 + formaldehyde + succinate + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown.

Cofactors or Prosthetic Groups: Fe2+ [Trewick02]


Enzymatic reaction of: N1-methyladenine demethylase (AlkB repair system for alkylated DNA and RNA)

EC Number: 1.14.11.33

N1-methyladenine + 2-oxoglutarate + oxygen <=> adenine + CO2 + formaldehyde + succinate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown.

Alternative Substrates for N1-methyladenine: N3-methylthymine [Koivisto04 , Delaney04 , Falnes04a ] , N1-methylguanine [Koivisto04 , Delaney04 , Falnes04a ] , 3-ethylcytosine [Delaney05 , Mishina05 ] , 1-N6-ethanoadenine [Delaney04 ] , N3-propylcytosine [Koivisto03 ] , N1-propyladenine [Koivisto03 ] , N3-hydroxyethylcytosine [Koivisto03 ] , N3-hydroxypropylcytosine [Koivisto03 ] , N1-hydroxyethyladenine [Koivisto03 ] , N1-hydroxypropyladenine [Koivisto03 ] , 3-N4-ethenocytosine [Delaney05 ] , 1-ethyladenine [Duncan02 ] , N3-methylcytosine [Falnes02 , Trewick02 ]

Summary:
AlkB-mediated repair involves hydroxylation of a alkylation lesion coupled to decarboxylation of 2-oxoglutarate, an unusual repair mechanism that regenerates the intact, unmethylated base and releases the alkyl group as an aldehyde in a process called oxidative dealkylation [Trewick02, Falnes02].

The kinetics of this reaction have been studied using a fluorescence-based assay with the lesion incorporated into single- and double-stranded DNA [Roy07]. The kcat (min-1) and Km (μM) for the N1-methyladenine single-stranded DNA lesion are 3.7 and 5.4, respectively, and for the double-stranded lesion are 3.1 and 6.2, respectively [Roy07]. The kcat (min-1) and Km (μM) for the N3-methylcytosine single-stranded DNA lesion are 2.2 and 3.4, respectively, and for the double-stranded lesion are 3.3 and 9.3, respectively [Roy07].

AlkB is also able to repair 1-N6-ethanoadenine leaving a ring-opened aldehyde product [Frick07], as well as 1-N6-ethenoadenine [Delaney05, Mishina05] and 3-N4-ethenocytosine in another process containing epoxide and glycol intermediates with the final release of the unmodified base and glyoxal [Delaney05]. Intermediates of the repair reactions have been characterised after 'oxidation in crystallo' [Yi10a].

Cofactors or Prosthetic Groups: Fe2+ [Falnes02, Trewick02]

Inhibitors (Unknown Mechanism): 2-mercaptoglutarate [Welford03] , quercetin [Welford03]


Sequence Features

Feature Class Location Citations Comment
Mutagenesis-Variant 51
[Holland10, UniProt12b]
Alternate sequence: T → A; UniProt: Slighly reduced activity towards single-stranded DNA containing 1- methyladenine. Reduces affinity for undamaged DNA.
Mutagenesis-Variant 69
[Holland10, UniProt12b]
Alternate sequence: W → A; UniProt: Abolishes activity towards single- stranded DNA containing 1-methyladenine.
Amino-Acid-Sites-That-Bind 69
[UniProt10]
UniProt: Substrate;
Mutagenesis-Variant 76
[Holland10, UniProt12b]
Alternate sequence: Y → A; UniProt: Reduces affinity for damaged DNA and activity towards single-stranded DNA containing 1-methyladenine.
Protein-Segment 76 -> 78
[UniProt10a]
UniProt: Substrate binding; Sequence Annotation Type: region of interest;
Conserved-Region 113 -> 213
[UniProt10a]
UniProt: Fe2OG dioxygenase;
Protein-Segment 120 -> 122
[UniProt10a]
UniProt: Alpha-ketoglutarate binding; Sequence Annotation Type: region of interest;
Metal-Binding-Site 131
[UniProt10]
UniProt: Iron; catalytic;
Metal-Binding-Site 133
[UniProt10]
UniProt: Iron; catalytic;
Mutagenesis-Variant 135
[Holland10, UniProt12b]
Alternate sequence: D → A; UniProt: Abolishes activity towards single- stranded DNA containing 1-methyladenine. Alters substrate specificity, so that the enzyme gains activity towards single- stranded DNA containing 1-methylguanine.
Amino-Acid-Sites-That-Bind 135
[UniProt10]
UniProt: Substrate;
Mutagenesis-Variant 161
[Holland10, UniProt12b]
Alternate sequence: R → A; UniProt: No effect on enzyme activity. Decreases affinity for damaged DNA.
Amino-Acid-Sites-That-Bind 161
[UniProt10]
UniProt: Substrate;
Metal-Binding-Site 187
[UniProt10]
UniProt: Iron; catalytic;
Protein-Segment 204 -> 210
[UniProt10a]
UniProt: Alpha-ketoglutarate binding; Sequence Annotation Type: region of interest;


Gene Local Context (not to scale): ?

Transcription Units:

Notes:

History:
10/20/97 Gene b2212 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10037; confirmed by SwissProt match.


References

Aas03: Aas PA, Otterlei M, Falnes PO, Vagbo CB, Skorpen F, Akbari M, Sundheim O, Bjoras M, Slupphaug G, Seeberg E, Krokan HE (2003). "Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA." Nature 421(6925);859-63. PMID: 12594517

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Begley03: Begley TJ, Samson LD (2003). "Molecular biology: A fix for RNA." Nature 421(6925);795-6. PMID: 12594492

Begley03a: Begley TJ, Samson LD (2003). "AlkB mystery solved: oxidative demethylation of N1-methyladenine and N3-methylcytosine adducts by a direct reversal mechanism." Trends Biochem Sci 28(1);2-5. PMID: 12517444

Bleijlevens07: Bleijlevens B, Shivarattan T, Sedgwick B, Rigby SE, Matthews SJ (2007). "Replacement of non-heme Fe(II) with Cu(II) in the alpha-ketoglutarate dependent DNA repair enzyme AlkB: spectroscopic characterization of the active site." J Inorg Biochem 101(7);1043-8. PMID: 17553567

Bleijlevens08: Bleijlevens B, Shivarattan T, Flashman E, Yang Y, Simpson PJ, Koivisto P, Sedgwick B, Schofield CJ, Matthews SJ (2008). "Dynamic states of the DNA repair enzyme AlkB regulate product release." EMBO Rep 9(9);872-7. PMID: 18617893

Chen94e: Chen BJ, Carroll P, Samson L (1994). "The Escherichia coli AlkB protein protects human cells against alkylation-induced toxicity." J Bacteriol 176(20);6255-61. PMID: 7928996

Colombi97: Colombi D, Gomes SL (1997). "An alkB gene homolog is differentially transcribed during the Caulobacter crescentus cell cycle." J Bacteriol 179(10);3139-45. PMID: 9150207

Delaney04: Delaney JC, Essigmann JM (2004). "Mutagenesis, genotoxicity, and repair of 1-methyladenine, 3-alkylcytosines, 1-methylguanine, and 3-methylthymine in alkB Escherichia coli." Proc Natl Acad Sci U S A 101(39);14051-6. PMID: 15381779

Delaney05: Delaney JC, Smeester L, Wong C, Frick LE, Taghizadeh K, Wishnok JS, Drennan CL, Samson LD, Essigmann JM (2005). "AlkB reverses etheno DNA lesions caused by lipid oxidation in vitro and in vivo." Nat Struct Mol Biol 12(10);855-60. PMID: 16200073

Dinglay00: Dinglay S, Trewick SC, Lindahl T, Sedgwick B (2000). "Defective processing of methylated single-stranded DNA by E. coli AlkB mutants." Genes Dev 14(16);2097-105. PMID: 10950872

Dinglay98: Dinglay S, Gold B, Sedgwick B (1998). "Repair in Escherichia coli alkB mutants of abasic sites and 3-methyladenine residues in DNA." Mutat Res 407(2);109-16. PMID: 9637239

Drablos04: Drablos F, Feyzi E, Aas PA, Vaagbo CB, Kavli B, Bratlie MS, Pena-Diaz J, Otterlei M, Slupphaug G, Krokan HE (2004). "Alkylation damage in DNA and RNA--repair mechanisms and medical significance." DNA Repair (Amst) 3(11);1389-407. PMID: 15380096

Duncan02: Duncan T, Trewick SC, Koivisto P, Bates PA, Lindahl T, Sedgwick B (2002). "Reversal of DNA alkylation damage by two human dioxygenases." Proc Natl Acad Sci U S A 99(26);16660-5. PMID: 12486230

Fabisiewicz92: Fabisiewicz A, Janion C (1992). "Effect of heat shock on expression of proteins not involved in the heat-shock regulon." Eur J Biochem 209(2);549-53. PMID: 1425661

Falnes02: Falnes PO, Johansen RF, Seeberg E (2002). "AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli." Nature 419(6903);178-82. PMID: 12226668

Falnes03: Falnes PO, Rognes T (2003). "DNA repair by bacterial AlkB proteins." Res Microbiol 154(8);531-8. PMID: 14527653

Falnes04: Falnes PO, Bjoras M, Aas PA, Sundheim O, Seeberg E (2004). "Substrate specificities of bacterial and human AlkB proteins." Nucleic Acids Res 32(11);3456-61. PMID: 15229293

Falnes04a: Falnes PO (2004). "Repair of 3-methylthymine and 1-methylguanine lesions by bacterial and human AlkB proteins." Nucleic Acids Res 32(21);6260-7. PMID: 15576352

Falnes05: Falnes PO (2005). "RNA repair--the latest addition to the toolbox for macromolecular maintenance." RNA Biol 2(1);14-6. PMID: 17132930

Falnes07: Falnes PO, Klungland A, Alseth I (2007). "Repair of methyl lesions in DNA and RNA by oxidative demethylation." Neuroscience 145(4);1222-32. PMID: 17175108

Fram88: Fram RJ, Marinus MG, Volkert MR (1988). "Gene expression in E. coli after treatment with streptozotocin." Mutat Res 198(1);45-51. PMID: 2965298

Frick07: Frick LE, Delaney JC, Wong C, Drennan CL, Essigmann JM (2007). "Alleviation of 1,N6-ethanoadenine genotoxicity by the Escherichia coli adaptive response protein AlkB." Proc Natl Acad Sci U S A 104(3);755-60. PMID: 17213319

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Henshaw04: Henshaw TF, Feig M, Hausinger RP (2004). "Aberrant activity of the DNA repair enzyme AlkB." J Inorg Biochem 98(5);856-61. PMID: 15134932

Holland10: Holland PJ, Hollis T (2010). "Structural and mutational analysis of Escherichia coli AlkB provides insight into substrate specificity and DNA damage searching." PLoS One 5(1);e8680. PMID: 20084272

Janion06: Janion C (2006). "[Chemically methylated DNA repair in Escherichia coli--the role of alkB protein]." Postepy Biochem 52(3);239-46. PMID: 17201058

Jiricny02: Jiricny J (2002). "DNA repair: bioinformatics helps reverse methylation damage." Curr Biol 12(24);R846-8. PMID: 12498704

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Kataoka83: Kataoka H, Yamamoto Y, Sekiguchi M (1983). "A new gene (alkB) of Escherichia coli that controls sensitivity to methyl methane sulfonate." J Bacteriol 153(3);1301-7. PMID: 6337994

Kataoka85: Kataoka H, Sekiguchi M (1985). "Molecular cloning and characterization of the alkB gene of Escherichia coli." Mol Gen Genet 198(2);263-9. PMID: 3884973

Kim07g: Kim MY, Zhou X, Delaney JC, Taghizadeh K, Dedon PC, Essigmann JM, Wogan GN (2007). "AlkB influences the chloroacetaldehyde-induced mutation spectra and toxicity in the pSP189 supF shuttle vector." Chem Res Toxicol 20(8);1075-83. PMID: 17658757

Koivisto03: Koivisto P, Duncan T, Lindahl T, Sedgwick B (2003). "Minimal methylated substrate and extended substrate range of Escherichia coli AlkB protein, a 1-methyladenine-DNA dioxygenase." J Biol Chem 278(45);44348-54. PMID: 12944387

Koivisto04: Koivisto P, Robins P, Lindahl T, Sedgwick B (2004). "Demethylation of 3-methylthymine in DNA by bacterial and human DNA dioxygenases." J Biol Chem 279(39);40470-4. PMID: 15269201

Kondo86: Kondo H, Nakabeppu Y, Kataoka H, Kuhara S, Kawabata S, Sekiguchi M (1986). "Structure and expression of the alkB gene of Escherichia coli related to the repair of alkylated DNA." J Biol Chem 261(33);15772-7. PMID: 3536913

Margison02: Margison G (2002). "A new damage limitation exercise: ironing (Fe(II)) out minor DNA methylation lesions." DNA Repair (Amst) 1(12);1057-61. PMID: 12531015

Mishina03: Mishina Y, He C (2003). "Probing the structure and function of the Escherichia coli DNA alkylation repair AlkB protein through chemical cross-linking." J Am Chem Soc 125(29);8730-1. PMID: 12862460

Mishina04: Mishina Y, Chen LX, He C (2004). "Preparation and characterization of the native iron(II)-containing DNA repair AlkB protein directly from Escherichia coli." J Am Chem Soc 126(51);16930-6. PMID: 15612731

Mishina04a: Mishina Y, Lee CH, He C (2004). "Interaction of human and bacterial AlkB proteins with DNA as probed through chemical cross-linking studies." Nucleic Acids Res 32(4);1548-54. PMID: 15004242

Mishina05: Mishina Y, Yang CG, He C (2005). "Direct repair of the exocyclic DNA adduct 1,N6-ethenoadenine by the DNA repair AlkB proteins." J Am Chem Soc 127(42);14594-5. PMID: 16231911

Mishina06: Mishina Y, He C (2006). "Oxidative dealkylation DNA repair mediated by the mononuclear non-heme iron AlkB proteins." J Inorg Biochem 100(4);670-8. PMID: 16469386

Nieminuszczy06: Nieminuszczy J, Janion C, Grzesiuk E (2006). "Mutator specificity of Escherichia coli alkB117 allele." Acta Biochim Pol 53(2);425-8. PMID: 16733554

Nieminuszczy06a: Nieminuszczy J, Sikora A, Wrzesinski M, Janion C, Grzesiuk E (2006). "AlkB dioxygenase in preventing MMS-induced mutagenesis in Escherichia coli: effect of Pol V and AlkA proteins." DNA Repair (Amst) 5(2);181-8. PMID: 16226494

Ougland04: Ougland R, Zhang CM, Liiv A, Johansen RF, Seeberg E, Hou YM, Remme J, Falnes PO (2004). "AlkB restores the biological function of mRNA and tRNA inactivated by chemical methylation." Mol Cell 16(1);107-16. PMID: 15469826

Rebeck88: Rebeck GW, Coons S, Carroll P, Samson L (1988). "A second DNA methyltransferase repair enzyme in Escherichia coli." Proc Natl Acad Sci U S A 85(9);3039-43. PMID: 3283737

Roy07: Roy TW, Bhagwat AS (2007). "Kinetic studies of Escherichia coli AlkB using a new fluorescence-based assay for DNA demethylation." Nucleic Acids Res 35(21);e147. PMID: 18003660

Samson86: Samson L, Derfler B, Waldstein EA (1986). "Suppression of human DNA alkylation-repair defects by Escherichia coli DNA-repair genes." Proc Natl Acad Sci U S A 83(15);5607-10. PMID: 3526337

Sedgwick02: Sedgwick B, Lindahl T (2002). "Recent progress on the Ada response for inducible repair of DNA alkylation damage." Oncogene 21(58);8886-94. PMID: 12483506

Sedgwick04: Sedgwick B (2004). "Repairing DNA-methylation damage." Nat Rev Mol Cell Biol 5(2);148-57. PMID: 15040447

Sedgwick06: Sedgwick B, Robins P, Lindahl T (2006). "Direct removal of alkylation damage from DNA by AlkB and related DNA dioxygenases." Methods Enzymol 408;108-20. PMID: 16793366

Shivarattan05: Shivarattan T, Chen HA, Simpson P, Sedgwick B, Matthews S (2005). "Resonance assignments of Escherichia coli AlkB: a key 2-oxoglutarate and Fe(II) dependent dioxygenase of the adaptive DNA-repair response." J Biomol NMR 33(2);138. PMID: 16258838

Smirnova94: Smirnova GV, Oktyabrsky ON, Moshonkina EV, Zakirova NV (1994). "Induction of the alkylation-inducible aidB gene of Escherichia coli by cytoplasmic acidification and N-ethylmaleimide." Mutat Res 314(1);51-6. PMID: 7504191

Teo86: Teo I, Sedgwick B, Kilpatrick MW, McCarthy TV, Lindahl T (1986). "The intracellular signal for induction of resistance to alkylating agents in E. coli." Cell 45(2);315-24. PMID: 3009022

Trewick02: Trewick SC, Henshaw TF, Hausinger RP, Lindahl T, Sedgwick B (2002). "Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base damage." Nature 419(6903);174-8. PMID: 12226667

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Vasileva99: Vasil'eva SV, Makhova EV, Moshkovskaia EIu (1999). "[Expression and functions of adaptive response genes in Escherichia coli treated with mono- and bifunctional alkylating agents. Interference with SOS response]." Genetika 35(4);444-9. PMID: 10420268

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Volkert91: Volkert MR, Hajec LI (1991). "Molecular analysis of the aidD6::Mu d1 (bla lac) fusion mutation of Escherichia coli K12." Mol Gen Genet 229(2);319-23. PMID: 1921981

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Watanabe90: Watanabe K, Ohta T, Watanabe M, Kato T, Shirasu Y (1990). "Inhibition of induction of adaptive response by o-vanillin in Escherichia coli B." Mutat Res 243(4);273-80. PMID: 2109194

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Yu06c: Yu B, Edstrom WC, Benach J, Hamuro Y, Weber PC, Gibney BR, Hunt JF (2006). "Crystal structures of catalytic complexes of the oxidative DNA/RNA repair enzyme AlkB." Nature 439(7078);879-84. PMID: 16482161

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Other References Related to Gene Regulation

Landini95: Landini P, Volkert MR (1995). "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." J Biol Chem 1995;270(14);8285-9. PMID: 7713936

Landini95a: Landini P, Volkert MR (1995). "RNA polymerase alpha subunit binding site in positively controlled promoters: a new model for RNA polymerase-promoter interaction and transcriptional activation in the Escherichia coli ada and aidB genes." EMBO J 14(17);4329-35. PMID: 7556074

Landini99: Landini P, Busby SJ (1999). "The Escherichia coli Ada protein can interact with two distinct determinants in the sigma70 subunit of RNA polymerase according to promoter architecture: identification of the target of Ada activation at the alkA promoter." J Bacteriol 181(5);1524-9. PMID: 10049384

Nakabeppu86: Nakabeppu Y, Sekiguchi M (1986). "Regulatory mechanisms for induction of synthesis of repair enzymes in response to alkylating agents: ada protein acts as a transcriptional regulator." Proc Natl Acad Sci U S A 83(17);6297-301. PMID: 3529081

Nakamura88: Nakamura T, Tokumoto Y, Sakumi K, Koike G, Nakabeppu Y, Sekiguchi M (1988). "Expression of the ada gene of Escherichia coli in response to alkylating agents. Identification of transcriptional regulatory elements." J Mol Biol 202(3);483-94. PMID: 3139888

Saget94: Saget BM, Walker GC (1994). "The Ada protein acts as both a positive and a negative modulator of Escherichia coli's response to methylating agents." Proc Natl Acad Sci U S A 1994;91(21);9730-4. PMID: 7937881

Saget95: Saget BM, Shevell DE, Walker GC (1995). "Alteration of lysine 178 in the hinge region of the Escherichia coli ada protein interferes with activation of ada, but not alkA, transcription." J Bacteriol 177(5);1268-74. PMID: 7868601

Sakumi89: Sakumi K, Sekiguchi M (1989). "Regulation of expression of the ada gene controlling the adaptive response. Interactions with the ada promoter of the Ada protein and RNA polymerase." J Mol Biol 1989;205(2);373-85. PMID: 2648001

Sakumi93a: Sakumi K, Igarashi K, Sekiguchi M, Ishihama A (1993). "The Ada protein is a class I transcription factor of Escherichia coli." J Bacteriol 175(8);2455-7. PMID: 8468304

Taketomi96: Taketomi A, Nakabeppu Y, Ihara K, Hart DJ, Furuichi M, Sekiguchi M (1996). "Requirement for two conserved cysteine residues in the Ada protein of Escherichia coli for transactivation of the ada promoter." Mol Gen Genet 250(5);523-32. PMID: 8676855


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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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