alkB

Summary

Gene Symbol: alkB
Description: oxidative demethylase of N1-methyladenine or N3-methylcytosine DNA lesions
Alias: ECK2204, JW2200, aidD
Species: Escherichia coli str. K-12 substr. MG1655

Top Publications

  1. ncbi Recent progress on the Ada response for inducible repair of DNA alkylation damage
    Barbara Sedgwick
    Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
    Oncogene 21:8886-94. 2002
  2. ncbi Incorporation of oxygen into the succinate co-product of iron(II) and 2-oxoglutarate dependent oxygenases from bacteria, plants and humans
    Richard W D Welford
    UC Berkeley, Department of Chemistry, Berkeley, CA 94720, USA
    FEBS Lett 579:5170-4. 2005
  3. ncbi Repair of methyl lesions in DNA and RNA by oxidative demethylation
    P Ø Falnes
    Department of Molecular Biosciences, University of Oslo, P O Box 1041 Blindern, N 0316 Oslo, Norway
    Neuroscience 145:1222-32. 2007
  4. ncbi AlkB restores the biological function of mRNA and tRNA inactivated by chemical methylation
    Rune Ougland
    Centre for Molecular Biology and Neuroscience and Institute of Medical Microbiology, Rikshospitalet University Hospital, NO 0027 Oslo, Norway
    Mol Cell 16:107-16. 2004
  5. ncbi Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA
    Per Arne Aas
    Institute of Cancer Research and Molecular Biology, Norwegian University of Science and Technology, N 7489 Trondheim, Norway
    Nature 421:859-63. 2003
  6. ncbi Probing the structure and function of the Escherichia coli DNA alkylation repair AlkB protein through chemical cross-linking
    Yukiko Mishina
    Department of Chemistry, The University of Chicago, 5735 South Ellis Avenue, Chicago, Illinois 60637, USA
    J Am Chem Soc 125:8730-1. 2003
  7. ncbi Minimal methylated substrate and extended substrate range of Escherichia coli AlkB protein, a 1-methyladenine-DNA dioxygenase
    Pertti Koivisto
    Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, United Kingdom
    J Biol Chem 278:44348-54. 2003
  8. ncbi AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli
    Pål Ø Falnes
    Centre for Molecular Biology and Neuroscience, and Institute of Medical Microbiology, University of Oslo, National Hospital, 0027 Oslo, Norway
    Nature 419:178-82. 2002
  9. ncbi Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base damage
    Sarah C Trewick
    Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
    Nature 419:174-8. 2002
  10. ncbi DNA repair by bacterial AlkB proteins
    Pål Ø Falnes
    Centre for Molecular Biology and Neuroscience and Institute of Medical Microbiology, University of Oslo, Rikshospitalet, 0027 Oslo, Norway
    Res Microbiol 154:531-8. 2003

Research Grants

Scientific Experts

  • P Ø Falnes
  • C Janion
  • Geoff Margison
  • J Jiricny
  • DOUGLAS F FIX
  • Barbara Sedgwick
  • Yukiko Mishina
  • Jadwiga Nieminuszczy
  • James C Delaney
  • Chuan He
  • Ottar Sundheim
  • Elzbieta Grzesiuk
  • John M Essigmann
  • Agnieszka M Maciejewska
  • Pertti Koivisto
  • Hans E Krokan
  • Geir Slupphaug
  • Cai Guang Yang
  • Boris Bleijlevens
  • Bomina Yu
  • Christopher J Schofield
  • Tara Shivarattan
  • Leona D Samson
  • Chengqi Yi
  • Per Arne Aas
  • Anna Sikora
  • Richard W D Welford
  • Thomas J Begley
  • Tomas Lindahl
  • Bogdan I Fedeles
  • Lauren E Frick
  • Emadoldin Feyzi
  • Cathrine B Vågbø
  • Finn Drabløs
  • Marit Otterlei
  • Timothy F Henshaw
  • Erwin van den Born
  • Xing Jian
  • Anna A Karkhanina
  • Marivi N Moen
  • Arne Klungland
  • Anders Bekkelund
  • Emily Flashman
  • Tod Duncan
  • Jeanette Ringvoll
  • Sarah C Trewick
  • S Dinglay
  • Steve J Matthews
  • John F Hunt
  • Peter C Dedon
  • Todd W Roy
  • Min Young Kim
  • Cintyu Wong
  • Kirsty S Hewitson
  • Koli Taghizadeh
  • Catherine L Drennan
  • Magnar Bjørås
  • Rune Ougland
  • Luke A McNeill
  • Erling Seeberg
  • Robert P Hausinger
  • Vipender Singh
  • Deyu Li
  • Zuzanna Kaczmarska
  • Agnieszka Polkowska-Nowakowska
  • Beata Krowisz
  • Jaroslaw Poznanski
  • Jaroslaw T Kusmierek
  • Y F Wei
  • Adam Nowicki
  • Beata Sokołowska
  • Jarosław T Kuśmierek
  • Guifang Jia
  • Michal Wrzesinski
  • Damian Mielecki
  • Qing Dai
  • Aleksandra Chojnacka
  • Wen Zhang
  • Guanhua Hou
  • Qiang Cui
  • Guanqun Zheng
  • Svetlana M Krylova
  • Michael U Musheev
  • Marina V Omelchenko
  • Jasmin Mecinovic
  • Sergey N Krylov
  • Alexander P Petrov
  • Cathrine Broberg Vågbø
  • Lisiane B Meira
  • Pete J Simpson

Detail Information

Publications79

  1. ncbi Recent progress on the Ada response for inducible repair of DNA alkylation damage
    Barbara Sedgwick
    Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
    Oncogene 21:8886-94. 2002
  2. ncbi Incorporation of oxygen into the succinate co-product of iron(II) and 2-oxoglutarate dependent oxygenases from bacteria, plants and humans
    Richard W D Welford
    UC Berkeley, Department of Chemistry, Berkeley, CA 94720, USA
    FEBS Lett 579:5170-4. 2005
    ..Here, we demonstrate that five members of the 2OG oxygenase family, AlkB from Escherichia coli, anthocyanidin synthase and flavonol synthase from Arabidopsis thaliana, and prolyl ..
  3. ncbi Repair of methyl lesions in DNA and RNA by oxidative demethylation
    P Ø Falnes
    Department of Molecular Biosciences, University of Oslo, P O Box 1041 Blindern, N 0316 Oslo, Norway
    Neuroscience 145:1222-32. 2007
    ..A few years ago, it was discovered that the E. coli AlkB protein represented an iron and 2-oxoglutarate dependent oxygenase capable of repairing methyl lesions in DNA by a ..
  4. ncbi AlkB restores the biological function of mRNA and tRNA inactivated by chemical methylation
    Rune Ougland
    Centre for Molecular Biology and Neuroscience and Institute of Medical Microbiology, Rikshospitalet University Hospital, NO 0027 Oslo, Norway
    Mol Cell 16:107-16. 2004
    ..It was recently demonstrated that the E. coli AlkB protein and a human homolog, hABH3, can demethylate these lesions both in DNA and RNA...
  5. ncbi Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA
    Per Arne Aas
    Institute of Cancer Research and Molecular Biology, Norwegian University of Science and Technology, N 7489 Trondheim, Norway
    Nature 421:859-63. 2003
    ..including damage reversal by oxidative demethylation of 1-methyladenine and 3-methylcytosine by Escherichia coli AlkB. By contrast, little is known about consequences and cellular handling of alkylation damage to RNA...
  6. ncbi Probing the structure and function of the Escherichia coli DNA alkylation repair AlkB protein through chemical cross-linking
    Yukiko Mishina
    Department of Chemistry, The University of Chicago, 5735 South Ellis Avenue, Chicago, Illinois 60637, USA
    J Am Chem Soc 125:8730-1. 2003
    Engineering chemical cross-linking groups at the protein/DNA interface provide a powerful method for probing the putative active site and a damage searching mechanism of the Escherichia coli alkylation DNA repair protein AlkB.
  7. ncbi Minimal methylated substrate and extended substrate range of Escherichia coli AlkB protein, a 1-methyladenine-DNA dioxygenase
    Pertti Koivisto
    Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, United Kingdom
    J Biol Chem 278:44348-54. 2003
    The Escherichia coli AlkB protein, and two human homologs ABH2 and ABH3, directly demethylate 1-methyladenine and 3-methylcytosine in DNA...
  8. ncbi AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli
    Pål Ø Falnes
    Centre for Molecular Biology and Neuroscience, and Institute of Medical Microbiology, University of Oslo, National Hospital, 0027 Oslo, Norway
    Nature 419:178-82. 2002
    The bacterial AlkB protein is known to be involved in cellular recovery from alkylation damage; however, the function of this protein remains unknown...
  9. ncbi Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base damage
    Sarah C Trewick
    Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
    Nature 419:174-8. 2002
    ..Here we report that the highly conserved AlkB protein repairs DNA alkylation damage by means of an unprecedented mechanism...
  10. ncbi DNA repair by bacterial AlkB proteins
    Pål Ø Falnes
    Centre for Molecular Biology and Neuroscience and Institute of Medical Microbiology, University of Oslo, Rikshospitalet, 0027 Oslo, Norway
    Res Microbiol 154:531-8. 2003
    The Escherichia coli AlkB protein is an iron- and 2-oxoglutarate-dependent oxygenase, repairing 1-methyladenine and 3-methylcytosine lesions in DNA...
  11. ncbi Repairing DNA-methylation damage
    Barbara Sedgwick
    Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, UK
    Nat Rev Mol Cell Biol 5:148-57. 2004
    ..The Escherichia coli AlkB dioxygenase and the two human homologues, ABH2 and ABH3, represent a novel mechanism of DNA repair...
  12. pmc Substrate specificities of bacterial and human AlkB proteins
    Pål Ø Falnes
    Centre for Molecular Biology and Neuroscience, Institute of Medical Microbiology, Rikshospitalet University Hospital, 0027 Oslo, Norway
    Nucleic Acids Res 32:3456-61. 2004
    ..3-methylcytosine (3-meC) residues into nucleic acids, and it was recently demonstrated that the Escherichia coli AlkB protein and two human homologues, hABH2 and hABH3, can remove these lesions from DNA by oxidative demethylation...
  13. ncbi Demethylation of 3-methylthymine in DNA by bacterial and human DNA dioxygenases
    Pertti Koivisto
    Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, United Kingdom
    J Biol Chem 279:40470-4. 2004
    ..The Escherichia coli AlkB and human ABH3 proteins repaired 3-methylthymine in both single-stranded and double-stranded polydeoxynucleotides, ..
  14. ncbi Alkylation damage in DNA and RNA--repair mechanisms and medical significance
    Finn Drabløs
    Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, N 7489 Trondheim, Norway
    DNA Repair (Amst) 3:1389-407. 2004
    ..g. XPF-ERCC1) for incision and homologous recombination to complete repair. Recently, Escherichia coli protein AlkB and human homologues were shown to be oxidative demethylases that repair cytotoxic 1-methyladenine (1-meA) and 3-..
  15. pmc Mutagenesis, genotoxicity, and repair of 1-methyladenine, 3-alkylcytosines, 1-methylguanine, and 3-methylthymine in alkB Escherichia coli
    James C Delaney
    Department of Chemistry and Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 101:14051-6. 2004
    b>AlkB repairs 1-alkyladenine and 3-methylcytosine lesions in DNA by directly reversing the base damage...
  16. pmc Repair of 3-methylthymine and 1-methylguanine lesions by bacterial and human AlkB proteins
    Pål Ø Falnes
    Department of Molecular Biosciences, University of Oslo, Postboks 1041, Blindern, 0316 Oslo, Norway
    Nucleic Acids Res 32:6260-7. 2004
    The Escherichia coli AlkB protein repairs 1-methyladenine (1-meA) and 3-methylcytosine (3-meC) lesions in DNA and RNA by oxidative demethylation, a reaction requiring ferrous iron and 2-oxoglutarate as cofactor and co-substrate, ..
  17. ncbi AlkB reverses etheno DNA lesions caused by lipid oxidation in vitro and in vivo
    James C Delaney
    Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nat Struct Mol Biol 12:855-60. 2005
    ..Here we show that the newly characterized enzyme AlkB repairs epsilonA and epsilonC...
  18. pmc Enzymological and structural studies of the mechanism of promiscuous substrate recognition by the oxidative DNA repair enzyme AlkB
    Bomina Yu
    Department of Biological Sciences, 702A Fairchild Center, MC2434, Columbia University, New York, NY 10027, USA
    Proc Natl Acad Sci U S A 106:14315-20. 2009
    ..and crystallographic studies of the mechanisms underlying promiscuous substrate recognition by Escherichia coli AlkB, a DNA repair enzyme that removes methyl adducts and some larger alkylation lesions from endocyclic positions on ..
  19. pmc Direct repair of the exocyclic DNA adduct 1,N6-ethenoadenine by the DNA repair AlkB proteins
    Yukiko Mishina
    Department of Chemistry, The University of Chicago, Illinois 60637, USA
    J Am Chem Soc 127:14594-5. 2005
    The exocyclic DNA base adduct 1,N6-ethenoadenine (epsilonA) is directly repaired by the AlkB proteins in vitro.
  20. ncbi Crystal structures of catalytic complexes of the oxidative DNA/RNA repair enzyme AlkB
    Bomina Yu
    Department of Biological Sciences and Northeast Structural Genomics Consortium, 702A Fairchild Center, MC2434, Columbia University, New York, New York 10027, USA
    Nature 439:879-84. 2006
    ..Escherichia coli AlkB and the homologous human proteins ABH2 and ABH3 (refs 5, 7) promiscuously repair DNA and RNA bases damaged by S(N)2 ..
  21. pmc Human ABH3 structure and key residues for oxidative demethylation to reverse DNA/RNA damage
    Ottar Sundheim
    Department of Cancer Research and Molecular Medicine, NTNU, Trondheim, Norway
    EMBO J 25:3389-97. 2006
    ..These lesions are directly reversed by ABH3 (hABH3) in humans and AlkB in Escherichia coli...
  22. pmc Alleviation of 1,N6-ethanoadenine genotoxicity by the Escherichia coli adaptive response protein AlkB
    Lauren E Frick
    Biological Engineering Division, Center for Environmental Health Sciences, and Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 104:755-60. 2007
    ..Here we show that an enzyme mechanistically unrelated to DNA glycosylases, the adaptive response protein AlkB, is capable of acting on EA via its canonical mechanism of oxidative dealkylation...
  23. ncbi AlkB influences the chloroacetaldehyde-induced mutation spectra and toxicity in the pSP189 supF shuttle vector
    Min Young Kim
    Department of Biological Engineering, Center for Environmental Health Sciences, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Chem Res Toxicol 20:1075-83. 2007
    ..b>AlkB, an iron-/alpha-ketoglutarate-dependent dioxygenase, repairs 1, N (6)-ethenodeoxyadenosine (A) and 3, N (4)-..
  24. ncbi Preparation and characterization of the native iron(II)-containing DNA repair AlkB protein directly from Escherichia coli
    Yukiko Mishina
    Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA
    J Am Chem Soc 126:16930-6. 2004
    The Escherichia coli AlkB protein was recently found to repair cytotoxic DNA lesions 1-methyladenine and 3-methylcytosine by using a novel iron-catalyzed oxidative demethylation mechanism...
  25. pmc Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA
    Cai Guang Yang
    Department of Chemistry, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA
    Nature 452:961-5. 2008
    Escherichia coli AlkB and its human homologues ABH2 and ABH3 repair DNA/RNA base lesions by using a direct oxidative dealkylation mechanism...
  26. pmc AlkB homologue 2-mediated repair of ethenoadenine lesions in mammalian DNA
    Jeanette Ringvoll
    Centre for Molecular Biology and Neuroscience, Institute of Medical Microbiology, Rikshospitalet HF and University of Oslo, Blindern, Oslo, Norway
    Cancer Res 68:4142-9. 2008
    ..the principal repair system for epsilon A lesions until recently, when it was shown that the Escherichia coli AlkB dioxygenase could directly reverse the damage...
  27. pmc Defective processing of methylated single-stranded DNA by E. coli AlkB mutants
    S Dinglay
    Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
    Genes Dev 14:2097-105. 2000
    Escherichia coli alkB mutants are very sensitive to DNA methylating agents. Despite these mutants being the subject of many studies, no DNA repair or other function has been assigned to the AlkB protein or to its human homolog...
  28. pmc Reversal of DNA alkylation damage by two human dioxygenases
    Tod Duncan
    Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, United Kingdom
    Proc Natl Acad Sci U S A 99:16660-5. 2002
    The Escherichia coli AlkB protein protects against the cytotoxicity of methylating agents by repair of the DNA lesions 1-methyladenine and 3-methylcytosine, which are generated in single-stranded stretches of DNA...
  29. ncbi The selectivity and inhibition of AlkB
    Richard W D Welford
    Dyson Perrins Laboratory and The Oxford Centre for Molecular Sciences, United Kingdom
    J Biol Chem 278:10157-61. 2003
    b>AlkB is one of four proteins involved in the adaptive response to DNA alkylation damage in Escherichia coli and is highly conserved from bacteria to humans...
  30. pmc The AlkB Family of Fe(II)/α-Ketoglutarate-dependent Dioxygenases: Repairing Nucleic Acid Alkylation Damage and Beyond
    Bogdan I Fedeles
    From the Departments of Chemistry and Biological Engineering and the Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
    J Biol Chem 290:20734-42. 2015
    The AlkB family of Fe(II)- and α-ketoglutarate-dependent dioxygenases is a class of ubiquitous direct reversal DNA repair enzymes that remove alkyl adducts from nucleobases by oxidative dealkylation...
  31. pmc Iron-catalysed oxidation intermediates captured in a DNA repair dioxygenase
    Chengqi Yi
    Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA
    Nature 468:330-3. 2010
    ..Escherichia coli AlkB is the first such enzyme that was discovered to repair methylated nucleic acids, which are otherwise cytotoxic and/..
  32. pmc AlkB dioxygenase preferentially repairs protonated substrates: specificity against exocyclic adducts and molecular mechanism of action
    Agnieszka M Maciejewska
    Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02 106 Warsaw, Poland
    J Biol Chem 288:432-41. 2013
    Efficient repair by Escherichia coli AlkB dioxygenase of exocyclic DNA adducts 3,N(4)-ethenocytosine, 1,N(6)-ethenoadenine, 3,N(4)-α-hydroxyethanocytosine, and reported here for the first time 3,N(4)-α-hydroxypropanocytosine requires ..
  33. ncbi The intracellular signal for induction of resistance to alkylating agents in E. coli
    I Teo
    Cell 45:315-24. 1986
    The E. coli ada gene positively controls its own expression and that of other genes (alkA, alkB, aidB) involved in repair of DNA alkylation damage...
  34. ncbi Mutator specificity of Escherichia coli alkB117 allele
    Jadwiga Nieminuszczy
    Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warszawa, Poland
    Acta Biochim Pol 53:425-8. 2006
    The Escherichia coli AlkB protein encoded by alkB gene was recently found to repair cytotoxic DNA lesions 1-methyladenine (1-meA) and 3-methylcytosine (3-meC) by using a novel iron-catalysed oxidative demethylation mechanism that protects ..
  35. ncbi A new damage limitation exercise: ironing (Fe(II)) out minor DNA methylation lesions
    Geoff Margison
    Cancer Research UK Carcinogenesis Group, Paterson Institute for Cancer Research, Christie Hospital Trust, Manchester, M20 4BX, UK
    DNA Repair (Amst) 1:1057-61. 2002
  36. ncbi Direct removal of alkylation damage from DNA by AlkB and related DNA dioxygenases
    Barbara Sedgwick
    London Research Institute, Cancer Research United Kingdom, Clare Hall Laboratories, South Mimms, Hertfordshire
    Methods Enzymol 408:108-20. 2006
    ..and 3-methylcytosine are removed efficiently from DNA by direct damage reversal, catalyzed by the Escherichia coli AlkB protein and its human homologs ABH2 and ABH3...
  37. ncbi RNA repair--the latest addition to the toolbox for macromolecular maintenance
    Pål Ø Falnes
    Department of Molecular Biosciences, University of Oslo, Oslo 0316 Norway
    RNA Biol 2:14-6. 2005
    ..In addition, recent studies indicate that RNA is also repaired. AlkB proteins, which were initially found to repair chemically alkylated DNA, can also remove alkyl lesions from RNA, ..
  38. pmc A second DNA methyltransferase repair enzyme in Escherichia coli
    G W Rebeck
    Charles A Dana Laboratory of Toxicology, Harvard School of Public Health, Boston, MA 02115
    Proc Natl Acad Sci U S A 85:3039-43. 1988
    The Escherichia coli ada-alkB operon encodes a 39-kDa protein (Ada) that is a DNA-repair methyltransferase and a 27-kDa protein (AlkB) of unknown function. By DNA blot hybridization analysis we show that the alkylation-sensitive E...
  39. ncbi Adaptive response of Escherichia coli to alkylation damage
    M R Volkert
    Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester 01655
    Environ Mol Mutagen 11:241-55. 1988
    ..Four genes have been identified as components of this response, ada, alkA, alkB and aidB. The functions of two of these genes are known...
  40. pmc Escherichia coli gene induction by alkylation treatment
    M R Volkert
    Genetics 112:11-26. 1986
    ..alkA, aidB and aidD are induced by both agents and appear to be regulated by ada. Neither aidC nor aidI is regulated by ada...
  41. ncbi Bacterial DNA repair genes and their eukaryotic homologues: 3. AlkB dioxygenase and Ada methyltransferase in the direct repair of alkylated DNA
    Jadwiga Nieminuszczy
    Department of Molecular Biology, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warszawa, Poland
    Acta Biochim Pol 54:459-68. 2007
    ..The Ada response includes the expression of four genes: ada, alkA, alkB, and aidB. The product of ada gene, Ada protein, is an activator of transcription of all four genes...
  42. pmc Kinetic studies of Escherichia coli AlkB using a new fluorescence-based assay for DNA demethylation
    Todd W Roy
    Department of Chemistry, Wayne State University, Detroit, MI 48202, USA
    Nucleic Acids Res 35:e147. 2007
    The Escherichia coli AlkB protein catalyzes the direct reversal of alkylation damage to DNA; primarily 1-methyladenine (1mA) and 3-methylcytosine (3mC) lesions created by endogenous or environmental alkylating agents...
  43. ncbi RNA base damage and repair
    Emadoldin Feyzi
    Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, N 7489 Trondheim, Norway
    Curr Pharm Biotechnol 8:326-31. 2007
    ..Finally, recent reports on repair of chemically methylated RNA by AlkB and a human homologue (hABH3) in vitro and in vivo strengthen the idea of RNA base repair as a cellular defence ..
  44. pmc Transcription increases methylmethane sulfonate-induced mutations in alkB strains of Escherichia coli
    Douglas Fix
    Department of Microbiology, Southern Illinois University, Carbondale, IL 62901, USA
    DNA Repair (Amst) 7:1289-97. 2008
    ..The repair of m3C in Escherichia coli is mediated by AlkB through oxidative demethylation and in the absence of repair, m3C leads to base-substitution mutations...
  45. ncbi Gene expression in E. coli after treatment with streptozotocin
    R J Fram
    Departments of Medicine, University of Massachusetts Medical School, Worcester 01605
    Mutat Res 198:45-51. 1988
    ..Induction of aidD, alkA, aidB, and sfiA expression occurs with all 3 agents although at markedly lower concentrations of MNNG and STZ ..
  46. pmc Dynamic states of the DNA repair enzyme AlkB regulate product release
    Boris Bleijlevens
    Division of Molecular Biosciences, Faculty of Natural Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK
    EMBO Rep 9:872-7. 2008
    The 2-oxoglutarate (2OG)- and Fe(2+)-dependent dioxygenase AlkB couples the demethylation of modified DNA to the decarboxylation of 2OG...
  47. doi AlkB demethylases flip out in different ways
    Ottar Sundheim
    Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Erling Skjalgssons gate 1, Trondheim, Norway
    DNA Repair (Amst) 7:1916-23. 2008
    ..by base excision repair (BER) and direct repair by a methyltransferase or by an oxidative demethylase of the AlkB type. Yang et al...
  48. doi Direct analysis of enzyme-catalyzed DNA demethylation
    Anna A Karkhanina
    Department of Chemistry, York University, Toronto, Ontario M3J 1P3, Canada
    Anal Chem 81:5871-5. 2009
    ..We then used this approach to study the kinetics of AlkB-catalyzed DNA demethylation and screen a number of potential inhibitors of this reaction...
  49. pmc Bioinformatics and functional analysis define four distinct groups of AlkB DNA-dioxygenases in bacteria
    Erwin van den Born
    Department of Molecular Biosciences, University of Oslo, PO Box 1041 Blindern, 0316 Oslo, Norway
    Nucleic Acids Res 37:7124-36. 2009
    The iron(II)- and 2-oxoglutarate (2OG)-dependent dioxygenase AlkB from Escherichia coli (EcAlkB) repairs alkylation damage in DNA by direct reversal...
  50. ncbi Inhibition of induction of adaptive response by o-vanillin in Escherichia coli B
    K Watanabe
    Institute of Environmental Toxicology, Tokyo, Japan
    Mutat Res 243:273-80. 1990
    ..coli B. The enhancement was also observed in uvrA, umuC, recA, polA, or alkB mutants. This effect was lower in an alkA mutant, but was restored in an alkA umuC double mutant...
  51. doi The role of AlkB protein in repair of 1,N⁶-ethenoadenine in Escherichia coli cells
    Agnieszka M Maciejewska
    Institute of Biochemistry and Biophysics, Department of Molecular Biology, Polish Academy of Sciences, 5A Pawinskiego Street, 02 106 Warsaw, Poland
    Mutagenesis 26:401-6. 2011
    ..of vinyl chloride, chloroacetaldehyde (CAA), but eliminates its cytotoxicity, we studied the participation of alkA, alkB and mug gene products in the repair of εA in Escherichia coli cells...
  52. ncbi Induction of the alkylation-inducible aidB gene of Escherichia coli by cytoplasmic acidification and N-ethylmaleimide
    G V Smirnova
    Laboratory of Physiology of Microorganisms, Russian Academy of Sciences, Perm
    Mutat Res 314:51-6. 1994
    ..influence of thiol reagents on the induction of the DNA damage-inducible genes of Escherichia coli, aidB, alkA, and alkB. Under aerobic conditions in the absence of alkylating agents aidB, but not alkA or alkB, was induced by an ..
  53. ncbi [Expression and functions of adaptive response genes in Escherichia coli treated with mono- and bifunctional alkylating agents. Interference with SOS response]
    S V Vasil'eva
    Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Moscow, Russia
    Genetika 35:444-9. 1999
    ..The functional specificity of the alkA, alkB, and aidB1 genes concerning both the structure and volume of DNA alkylation and the specificity of cell ..
  54. pmc Interaction of human and bacterial AlkB proteins with DNA as probed through chemical cross-linking studies
    Yukiko Mishina
    Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA
    Nucleic Acids Res 32:1548-54. 2004
    The Escherichia coli AlkB protein was recently found to repair cytotoxic DNA lesions 1-methyladenine and 3-methylcytosine by using a novel iron-catalyzed oxidative demethylation mechanism...
  55. ncbi DNA repair: bioinformatics helps reverse methylation damage
    Josef Jiricny
    Institute of Medical Radiobiology of the University of Zurich and the Paul Scherrer Institute, August Forel Strasse 7, Ch 8008 Zurich, Switzerland
    Curr Biol 12:R846-8. 2002
    Recent work has uncovered a novel DNA repair enzyme: the AlkB protein of Escherichia coli, which oxidises the methyl groups of 1-methyladenine and 3-methylcytosine to hydroxymethyl moieties; the oxidised groups are subsequently released ..
  56. ncbi Aberrant activity of the DNA repair enzyme AlkB
    Timothy F Henshaw
    Department of Chemistry, Michigan State University, East Lansing, MI 48824 4320, USA
    J Inorg Biochem 98:856-61. 2004
    Escherichia coli AlkB is a DNA/RNA repair enzyme containing a mononuclear Fe(II) site that couples the oxidative decomposition of alpha-ketoglutarate (alphaKG) to the hydroxylation of 1-methyladenine or 3-methylcytosine lesions in DNA or ..
  57. pmc An alkB gene homolog is differentially transcribed during the Caulobacter crescentus cell cycle
    D Colombi
    Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, Brazil
    J Bacteriol 179:3139-45. 1997
    A Caulobacter crescentus alkB gene homolog was identified in a clone previously shown to contain the heat shock genes dnaK and dnaJ; the homolog is located upstream of dnaK and is transcribed in the opposite orientation...
  58. pmc Molecular cloning and functional analysis of a human cDNA encoding an Escherichia coli AlkB homolog, a protein involved in DNA alkylation damage repair
    Y F Wei
    Department of Molecular Biology, Human Genome Sciences Inc, Rockville, MD 20850 3338, USA
    Nucleic Acids Res 24:931-37. 1996
    The Escherichia coli AlkB protein is involved in protecting cells against mutation and cell death induced specifically by SN2-type alkylating agents such as methyl methanesulfonate (MMS)...
  59. ncbi Structure and expression of the alkB gene of Escherichia coli related to the repair of alkylated DNA
    H Kondo
    J Biol Chem 261:15772-7. 1986
    When the alkB gene of Escherichia coli that controls sensitivity of bacteria to methyl methanesulfonate was placed under the control of the lac regulatory region on a multicopy plasmid, the gene product, AlkB protein, was overproduced...
  60. pmc The Escherichia coli AlkB protein protects human cells against alkylation-induced toxicity
    B J Chen
    Harvard School of Public Health, Boston, Massachusetts 02115
    J Bacteriol 176:6255-61. 1994
    ..The alkylation-sensitive phenotype of E. coli alkB mutants marks the alkB pathway as an extremely effective defense mechanism against the cytotoxic effects of the SN2,..
  61. pmc Suppression of Escherichia coli alkB mutants by Saccharomyces cerevisiae genes
    Y F Wei
    Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts, USA
    J Bacteriol 177:5009-15. 1995
    The alkB gene is one of a group of alkylation-inducible genes in Escherichia coli, and its product protects cells from SN2-type alkylating agents such as methyl methanesulfonate (MMS)...
  62. pmc A new gene (alkB) of Escherichia coli that controls sensitivity to methyl methane sulfonate
    H Kataoka
    J Bacteriol 153:1301-7. 1983
    ..Another mutation was found near nalA, and the gene responsible was named alkB. Its phenotype was different from that of ada, since the alkB mutant exhibited a normal adaptive response to N-..
  63. ncbi AlkB mystery solved: oxidative demethylation of N1-methyladenine and N3-methylcytosine adducts by a direct reversal mechanism
    Thomas J Begley
    Biological Engineering Division and Center for Environmental Health Sciences, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Trends Biochem Sci 28:2-5. 2003
    ..For nearly two decades, we have known that the Escherichia coli alkB gene product protects against cell killing by S(N)2-alkylating agents, probably through DNA repair...
  64. pmc Active site and complete sequence of the suicidal methyltransferase that counters alkylation mutagenesis
    B Demple
    Proc Natl Acad Sci U S A 82:2688-92. 1985
    ..These same structural features are present at the active site of thymidylate synthase, suggesting a common chemical mechanism for activation of the cysteine...
  65. ncbi Molecular cloning and characterization of the alkB gene of Escherichia coli
    H Kataoka
    Mol Gen Genet 198:263-9. 1985
    ..we constructed hybrid plasmids that can suppress the increased methylmethane sulfonate sensitivity caused by alkB mutation...
  66. pmc Alkylating agents induce UVM, a recA-independent inducible mutagenic phenomenon in Escherichia coli
    G Wang
    Department of Microbiology and Molecular Genetics, UMD New Jersey Medical School, Newark 07103 2714, USA
    Genetics 141:813-23. 1995
    ..Our data show that MNNG induction of UVM is independent of ada, alkA and alkB genes and define UVM as an inducible mutagenic phenomenon distinct from the E. coli adaptive and SOS responses.
  67. doi Lethal and mutagenic properties of MMS-generated DNA lesions in Escherichia coli cells deficient in BER and AlkB-directed DNA repair
    Anna Sikora
    Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5A, 02 106 Warszawa, Poland
    Mutagenesis 25:139-47. 2010
    ..bases can be removed by a system of base excision repair (BER) and by oxidative DNA demethylation catalysed by AlkB protein...
  68. ncbi Molecular biology: A fix for RNA
    Thomas J Begley
    Nature 421:795-6. 2003
  69. ncbi Molecular analysis of the aidD6::Mu d1 (bla lac) fusion mutation of Escherichia coli K12
    M R Volkert
    Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester 01655
    Mol Gen Genet 229:319-23. 1991
    ..biochemical evidence indicating that the aidD6::Mu d1 (bla lac) fusion is an insertion of Mu d1 (bla lac) into the alkB coding sequence...
  70. ncbi Effect of heat shock on expression of proteins not involved in the heat-shock regulon
    A Fabisiewicz
    Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw
    Eur J Biochem 209:549-53. 1992
    ..the SOS response, was somewhat higher in the heat-shocked than in the non-shocked cells, whereas expression of ada, alkB and alkA genes, after induction of the adaptive response, was about the same...
  71. ncbi Expression of DNA damage-inducible genes of Escherichia coli upon treatment with methylating, ethylating and propylating agents
    M R Volkert
    Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester 01655
    Mutat Res 217:109-15. 1989
    ..We find that the Ada-regulated adaptive response genes (ada-alkB, alkA and aidB) are induced primarily in response to methylation treatment...
  72. ncbi [Chemically methylated DNA repair in Escherichia coli--the role of alkB protein]
    Celina Janion
    Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 5A Pawinskiego St, 02 106 Warszawa, Poland
    Postepy Biochem 52:239-46. 2006
    ..repaired by proteins and enzymes either permanently present in the cells (Ogt, Ada) or produced transiently (Ada, AlkB, AlkA, Aid), after induction of the Ada defence system...
  73. ncbi AlkB dioxygenase in preventing MMS-induced mutagenesis in Escherichia coli: effect of Pol V and AlkA proteins
    Jadwiga Nieminuszczy
    Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5A, 02 106 Warszawa, Poland
    DNA Repair (Amst) 5:181-8. 2006
    The deleterious effect of defective alkB allele encoding 1meA/3meC dioxygenase on reactivation of MMS-treated phage DNA has been frequently studied...
  74. ncbi Resonance assignments of Escherichia coli AlkB: a key 2-oxoglutarate and Fe(II) dependent dioxygenase of the adaptive DNA-repair response
    Tara Shivarattan
    J Biomol NMR 33:138. 2005
  75. pmc Oxidative dealkylation DNA repair mediated by the mononuclear non-heme iron AlkB proteins
    Yukiko Mishina
    Department of Chemistry, The University of Chicago, 5735 South Ellis Avenue, Chicago, IL 60637, USA
    J Inorg Biochem 100:670-8. 2006
    ..discovered that some of the alkylation DNA base damage can be directly removed by a family of proteins called the AlkB proteins that utilize a mononuclear non-heme iron(II) and alpha-ketoglutarate as cofactor and cosubstrate...
  76. ncbi Repair in Escherichia coli alkB mutants of abasic sites and 3-methyladenine residues in DNA
    S Dinglay
    Imperial Cancer Research Fund, Clare Hall Laboratories, Herts, UK
    Mutat Res 407:109-16. 1998
    Escherichia coli alkB mutants are sensitive to methyl methanesulfonate and dimethylsulphate, and are defective in the processing of methylated DNA. The function of the AlkB protein has not been determined...
  77. ncbi Replacement of non-heme Fe(II) with Cu(II) in the alpha-ketoglutarate dependent DNA repair enzyme AlkB: spectroscopic characterization of the active site
    Boris Bleijlevens
    Division of Molecular Biosciences, Faculty of Natural Sciences, Imperial College London, South Kensington Campus, Biochemistry Building, London SW7 2AZ, UK
    J Inorg Biochem 101:1043-8. 2007
    The bacterial DNA repair enzyme AlkB is an alpha-ketoglutarate (alphaKG) dependent non-heme Fe(II) containing dioxygenase. Here we describe, for the first time, the preparation of a Cu(II)-reconstituted form of AlkB in various complexes...

Research Grants1

  1. Contribution of DNA photoproducts to UV mutagenesis
    Douglas Fix; Fiscal Year: 2003
    ..Furthermore, these AREA-funded studies will provide valuable research experience for undergraduate students in the biological sciences. ..