NEIL2

Summary

Gene Symbol: NEIL2
Description: nei endonuclease VIII-like 2 (E. coli)
Alias: NEH2, NEI2, DNA glycosylase/AP lyase Neil2, DNA-(apurinic or apyrimidinic site) lyase Neil2, endonuclease 8-like 2, endonuclease VIII-like 2, nei homolog 2, nei like 2, nei-like protein 2
Species: human

Top Publications

  1. ncbi Acetylation of the human DNA glycosylase NEIL2 and inhibition of its activity
    Kishor K Bhakat
    Sealy Center for Molecular Science and Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, TX 77555 1079, USA
    Nucleic Acids Res 32:3033-9. 2004
  2. ncbi Functional variants of the NEIL1 and NEIL2 genes and risk and progression of squamous cell carcinoma of the oral cavity and oropharynx
    Xiadong Zhai
    Department of Epidemiology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Clin Cancer Res 14:4345-52. 2008
  3. ncbi Stimulation of NEIL2-mediated oxidized base excision repair via YB-1 interaction during oxidative stress
    Soumita Das
    Sealy Center for Molecular Medicine and Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555, USA
    J Biol Chem 282:28474-84. 2007
  4. ncbi AP endonuclease-independent DNA base excision repair in human cells
    Lee Wiederhold
    Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77555, USA
    Mol Cell 15:209-20. 2004
  5. ncbi Deficiency of the oxidative damage-specific DNA glycosylase NEIL1 leads to reduced germinal center B cell expansion
    Hiromi Mori
    Laboratory for Immune Diversity, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, 1 7 22 Suehiro cho, Tsurumi, Yokohama 230 0045, Japan
    DNA Repair (Amst) 8:1328-32. 2009
  6. ncbi Nucleotide, cytogenetic and expression impact of the human chromosome 8p23.1 inversion polymorphism
    Nina Bosch
    Genetic Causes of Disease Group, Genes and Disease Programme Center for Genomic Regulation CRG UPF, Barcelona, Catalonia, Spain
    PLoS ONE 4:e8269. 2009
  7. ncbi Discovery of the negative regulator of Nrf2, Keap1: a historical overview
    Ken Itoh
    Department of Stress Response Science, Hirosaki University Graduate School of Medicine, Japan
    Antioxid Redox Signal 13:1665-78. 2010
  8. ncbi Structural analysis of the complex of Keap1 with a prothymosin alpha peptide
    Balasundaram Padmanabhan
    Genomic Sciences Center, Yokohama Institute, RIKEN, 1 7 22 Suehiro cho, Tsurumi, Yokohama 230 0045, Japan
    Acta Crystallogr Sect F Struct Biol Cryst Commun 64:233-8. 2008
  9. ncbi Identification of the interactive interface and phylogenic conservation of the Nrf2-Keap1 system
    Makoto Kobayashi
    The Center for Tsukuba Advanced Research Alliance and Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba 305 8577, Japan
    Genes Cells 7:807-20. 2002
  10. ncbi Cul3-mediated Nrf2 ubiquitination and antioxidant response element (ARE) activation are dependent on the partial molar volume at position 151 of Keap1
    Aimee L Eggler
    Center for Pharmaceutical Biotechnology and the Department of Medicinal Chemistry and Pharmacognosy, University of Illinois, Chicago, IL 60607, USA
    Biochem J 422:171-80. 2009

Research Grants

  1. Repair of Oxidized Bases in Mammalian Genomes
    Sankar Mitra; Fiscal Year: 2010
  2. Repair of Oxidized Bases in Mammalian Genomes
    Sankar Mitra; Fiscal Year: 2007
  3. Repair of Oxidized Bases in Mammalian Genomes
    Sankar Mitra; Fiscal Year: 2009
  4. Repair of Oxidized Bases in Mammalian Genomes
    Sankar Mitra; Fiscal Year: 2010
  5. Regulation of Nrf2 Signaling
    Michael Freeman; Fiscal Year: 2009
  6. Mechanisms of Neurotoxicity of Combustion-smoke Inhalation to the Brain
    Ella W Englander; Fiscal Year: 2010
  7. HYPOXIA-INDUCED DNA DAMAGE AND REPAIR IN THE RAT BRAIN
    Ella Englander; Fiscal Year: 2009
  8. HYPOXIA-INDUCED DNA DAMAGE AND REPAIR IN THE RAT BRAIN
    Ella W Englander; Fiscal Year: 2010
  9. Repair of oxidative damage in mammalian genomes
    Tapas K Hazra; Fiscal Year: 2010
  10. Repair of oxidative damage in mammalian genomes
    TAPAS HAZRA; Fiscal Year: 2009

Scientific Experts

  • Michael McMahon
  • M Takao
  • TAPAS HAZRA
  • Ken Itoh
  • Takashi Kobunai
  • Aimee L Eggler
  • Yiguo Zhang
  • Peter Broderick
  • Ella Englander
  • Thomas A Rosenquist
  • Sampa Pal
  • Sankar Mitra
  • Michael Freeman
  • Masayuki Yamamoto
  • Kit I Tong
  • SYLVIE DOUBLIE
  • Balasundaram Padmanabhan
  • I R Grin
  • Aditi Das
  • Carla J Kinslow
  • Veslemøy Rolseth
  • Inga R Grin
  • Istvan Boldogh
  • Kishor K Bhakat
  • Hong Dou
  • Sherif Z Abdel-Rahman
  • D O Zharkov
  • Muralidhar L Hegde
  • Luisa Luna
  • Magnar Bjørås
  • Shigeyuki Yokoyama
  • Akira Kobayashi
  • Dmitry O Zharkov
  • Samuel H Wilson
  • Rajendra Prasad
  • Rowena Hancock
  • Ana I Rojo
  • Viswanath Bandaru
  • Lee Wiederhold
  • Huaxian Ma
  • Natalya A Smirnova
  • Keiko Taguchi
  • Meryl S Lillenes
  • Veron Ramsuran
  • X Y Goh
  • Yasutake Katoh
  • Minmin Liu
  • Nina Bosch
  • Jeffrey K Wickliffe
  • Courtney E Hill
  • Randa A El-Zein
  • Hiromi Mori
  • Silje Z Krokeide
  • G A Nevinsky
  • Pawel Jaruga
  • Miral Dizdaroglu
  • R Stephen Lloyd
  • A R Dallosso
  • Amit K Maiti
  • Ryan Holland
  • Elise Rundén-Pran
  • V S Sidorenko
  • Ole Petter Ottersen
  • Xiadong Zhai
  • N K Bernstein
  • Soumita Das
  • Flor M Perez Campo
  • Sevtap Savas
  • M Akbari
  • Laura M Roy
  • Toshiyuki Tanaka
  • Yoriko Watai
  • Jeffrey P Bond
  • Susan S Wallace
  • Feridoun Karimi-Busheri
  • Kimberly A Conlon
  • John B Leppard
  • M Katie Hailer
  • Michael Weinfeld
  • Padmini Kedar
  • Alan E Tomkinson
  • Donna D Zhang
  • Atsushi Katafuchi
  • David A Bloom
  • Albena T Dinkova-Kostova
  • Makoto Kobayashi
  • José Pedraza-Chaverri
  • Sandra Espada
  • Omar Noel Medina-Campos
  • Antonio Cuadrado

Detail Information

Publications69

  1. ncbi Acetylation of the human DNA glycosylase NEIL2 and inhibition of its activity
    Kishor K Bhakat
    Sealy Center for Molecular Science and Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, TX 77555 1079, USA
    Nucleic Acids Res 32:3033-9. 2004
    ..coactivator p300 stably interacts with, and acetylates, the recently discovered human DNA glycosylase NEIL2, involved in the repair of oxidized bases both in vivo and in vitro...
  2. ncbi Functional variants of the NEIL1 and NEIL2 genes and risk and progression of squamous cell carcinoma of the oral cavity and oropharynx
    Xiadong Zhai
    Department of Epidemiology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Clin Cancer Res 14:4345-52. 2008
    Human DNA glycosylases NEIL1 and NEIL2 participate in oxidized base excision repair and protect cells from DNA damage...
  3. ncbi Stimulation of NEIL2-mediated oxidized base excision repair via YB-1 interaction during oxidative stress
    Soumita Das
    Sealy Center for Molecular Medicine and Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555, USA
    J Biol Chem 282:28474-84. 2007
    The recently characterized enzyme NEIL2 (Nei-like-2), one of the four oxidized base-specific DNA glycosylases (OGG1, NTH1, NEIL1, and NEIL2) in mammalian cells, has poor base excision activity from duplex DNA...
  4. ncbi AP endonuclease-independent DNA base excision repair in human cells
    Lee Wiederhold
    Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77555, USA
    Mol Cell 15:209-20. 2004
    ..The recently discovered mammalian DNA glycosylase/AP lyases, NEIL1 and NEIL2, unlike the previously characterized OGG1 and NTH1, generate DNA strand breaks with 3' phosphate termini...
  5. ncbi Deficiency of the oxidative damage-specific DNA glycosylase NEIL1 leads to reduced germinal center B cell expansion
    Hiromi Mori
    Laboratory for Immune Diversity, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, 1 7 22 Suehiro cho, Tsurumi, Yokohama 230 0045, Japan
    DNA Repair (Amst) 8:1328-32. 2009
    Mammalian cells possess multiple DNA glycosylases, including OGG1, NTH1, NEIL1, NEIL2 and NEIL3, for the repair of oxidative DNA damage...
  6. ncbi Nucleotide, cytogenetic and expression impact of the human chromosome 8p23.1 inversion polymorphism
    Nina Bosch
    Genetic Causes of Disease Group, Genes and Disease Programme Center for Genomic Regulation CRG UPF, Barcelona, Catalonia, Spain
    PLoS ONE 4:e8269. 2009
    ..The identification of single nucleotide polymorphisms (SNPs) tightly linked to the genomic orientation of a given region should be useful to indirectly evaluate the genotypes of large genomic orientations in the individuals...
  7. ncbi Discovery of the negative regulator of Nrf2, Keap1: a historical overview
    Ken Itoh
    Department of Stress Response Science, Hirosaki University Graduate School of Medicine, Japan
    Antioxid Redox Signal 13:1665-78. 2010
    ..Keap1 suppresses Nrf2 activity by specifically binding to its evolutionarily conserved N-terminal Neh2 regulatory domain...
  8. ncbi Structural analysis of the complex of Keap1 with a prothymosin alpha peptide
    Balasundaram Padmanabhan
    Genomic Sciences Center, Yokohama Institute, RIKEN, 1 7 22 Suehiro cho, Tsurumi, Yokohama 230 0045, Japan
    Acta Crystallogr Sect F Struct Biol Cryst Commun 64:233-8. 2008
    ..which is formed by the double-glycine repeat and C-terminal region domains (Keap1-DC), interacts directly with the Neh2 domain of Nrf2...
  9. ncbi Identification of the interactive interface and phylogenic conservation of the Nrf2-Keap1 system
    Makoto Kobayashi
    The Center for Tsukuba Advanced Research Alliance and Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba 305 8577, Japan
    Genes Cells 7:807-20. 2002
    ..To gain an insight into our present enigma as to how cells receive oxidative and electrophilic signals and transduce them to Nrf2, we have developed a zebrafish model system for molecular toxicological studies...
  10. ncbi Cul3-mediated Nrf2 ubiquitination and antioxidant response element (ARE) activation are dependent on the partial molar volume at position 151 of Keap1
    Aimee L Eggler
    Center for Pharmaceutical Biotechnology and the Department of Medicinal Chemistry and Pharmacognosy, University of Illinois, Chicago, IL 60607, USA
    Biochem J 422:171-80. 2009
    ..This model has significant implications for how electrophiles which modify Cys(151), disrupt the repressive function of Keap1...
  11. ncbi Base excision repair activities in organotypic hippocampal slice cultures exposed to oxygen and glucose deprivation
    Veslemøy Rolseth
    Centre for Molecular Biology and Neuroscience, Institute of Medical Microbiology, University of Oslo, Rikshospitalet, N 0027 Oslo, Norway
    DNA Repair (Amst) 7:869-78. 2008
    ..Real-time RT-PCR showed that transcription of DNA glycosylases, including Ogg1, Nth1, Ung, Aag, Neil1 and Neil2 were not changed in response to OGD treatment (t=0 h)...
  12. ncbi Human Nei-like protein NEIL3 has AP lyase activity specific for single-stranded DNA and confers oxidative stress resistance in Escherichia coli mutant
    Masashi Takao
    Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, Aoba ku, Sendai, Japan
    Genes Cells 14:261-70. 2009
    ..damage to DNA, cells contain several DNA glycosylases including OGG1, NTH1 and the Nei-like proteins, NEIL1 and NEIL2. A third Nei-like protein, NEIL3, is composed of an amino-terminal Nei-like domain and an unknown carboxy-terminal ..
  13. ncbi Expression and purification of NEIL3, a human DNA glycosylase homolog
    Silje Z Krokeide
    Centre for Molecular Biology and Neuroscience, Department of Molecular Biology, Institute of Microbiology, Rikshospitalet Medical Centre, Sognsvannsveien 28, N0027 Oslo, Norway
    Protein Expr Purif 65:160-4. 2009
    ..Thus, a mammalian family of three proteins (NEIL1, NEIL2 and NEIL3) that showed homology to the Escherichia coli Fpg/Nei DNA glycosylases was identified...
  14. ncbi A simple method for amino acid selective isotope labeling of recombinant proteins in E. coli
    Kit I Tong
    Center for Tsukuba Advanced Research Alliance, Graduate School of Comprehensive Human Sciences, JST ERATO Environmental Response Project, University of Tsukuba, Tsukuba, 305 8577, Japan
    J Biomol NMR 42:59-67. 2008
    ..The sequential backbone resonance assignment of the Neh2 domain of Nrf2 transcriptional factor, an intrinsically disordered protein with high spectral degeneracy, was ..
  15. ncbi Polynucleotide kinase as a potential target for enhancing cytotoxicity by ionizing radiation and topoisomerase I inhibitors
    N K Bernstein
    Department of Biochemistry, University of Alberta, 11560 University Avenue, Edmonton, Alberta, Canada
    Anticancer Agents Med Chem 8:358-67. 2008
    ..agents including ionizing radiation, topoisomerase I inhibitors, and DNA repair glycosylases such as NEIL1 and NEIL2, often contain 5'-hydroxyl and/or 3'-phosphate termini...
  16. ncbi Structural insights into the similar modes of Nrf2 transcription factor recognition by the cytoplasmic repressor Keap1
    Balasundaram Padmanabhan
    Genomic Sciences Center, Yokohama Institute, RIKEN, 1 7 22 Suehiro cho, Tsurumi, Yokohama 230 0045, Japan
    J Synchrotron Radiat 15:273-6. 2008
    ..The Neh2 domain of Nrf2 interacts with Keap1 at the bottom region of the Kelch/beta-propeller domain which is formed by ..
  17. ncbi Prospective type 1 and type 2 disulfides of Keap1 protein
    Ryan Holland
    Department of Chemistry and Biochemistry, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, Maryland 21250, USA
    Chem Res Toxicol 21:2051-60. 2008
    ..The energy minimizations indicated marked alterations in structure with a substantial constriction of Neh2 binding domain of the Keap1 Kelch repeat domain...
  18. ncbi Novel DNA glycosylases from Mycobacterium tuberculosis
    V S Sidorenko
    Institute of Chemical Biology and Fundamental Medicine, Siberian Division of the Russian Academy of Sciences, Novosibirsk 630090, Russia
    Biochemistry (Mosc) 73:442-50. 2008
    ..We have cloned and expressed two paralogs (Mtu-Nei2 and Mtu-Fpg2) from 36KAZ and KHA94 isolates of Mycobacterium tuberculosis and studied their ability to participate ..
  19. ncbi Widespread distribution of DNA glycosylases removing oxidative DNA lesions in human and rodent brains
    Veslemøy Rolseth
    Centre for Molecular Biology and Neuroscience, Institute of Medical Microbiology, University of Oslo, Rikshospitalet HF, Oslo, Norway
    DNA Repair (Amst) 7:1578-88. 2008
    ..In mammalian cells at least five different DNA glycosylases with overlapping substrate specificity, NEIL1, NEIL2, NEIL3, OGG1 and NTH1, remove oxidative DNA base lesions...
  20. ncbi Mutator phenotype of mammalian cells due to deficiency of NEIL1 DNA glycosylase, an oxidized base-specific repair enzyme
    Amit K Maiti
    Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA
    DNA Repair (Amst) 7:1213-20. 2008
    The recently characterized NEIL1 and NEIL2 are distinct from the previously characterized mammalian DNA glycosylases (OGG1 and NTH1) involved in repair of oxidized bases because of the NEILs' preference for excising base lesions from ..
  21. ncbi Single nucleotide polymorphisms 5' upstream the coding region of the NEIL2 gene influence gene transcription levels and alter levels of genetic damage
    Carla J Kinslow
    Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, TX 77555 1110, USA
    Genes Chromosomes Cancer 47:923-32. 2008
    b>NEIL2 (EC 4.2.99.18), a mammalian DNA glycosylase and ortholog of the bacterial Fpg/Nei, excises oxidized DNA lesions from bubble or single-stranded structures, suggesting its involvement in transcription-coupled DNA repair...
  22. ncbi Heavy metal ions affect the activity of DNA glycosylases of the fpg family
    I R Grin
    Institute of Chemical Biology and Fundamental Medicine, Siberian Division of the Russian Academy of Sciences, pr Lavrentieva 8, Novosibirsk, Russia
    Biochemistry (Mosc) 74:1253-9. 2009
    ..enzymes formamidopyrimidine-DNA glycosylase (Fpg) and endonuclease VIII (Nei) and their eukaryotic homologs NEIL1, NEIL2, and NEIL3 define the Fpg family of DNA glycosylases, which initiate the process of repair of oxidized DNA bases...
  23. ncbi Signaling pathways activated by the phytochemical nordihydroguaiaretic acid contribute to a Keap1-independent regulation of Nrf2 stability: Role of glycogen synthase kinase-3
    Ana I Rojo
    Departamento de Bioquímica e Instituto de Investigaciones Biomédicas Alberto Sols UAM CSIC, Centro de Investigación en Red sobre Enfermedades Neurodegenerativas, Instituto de Investigación Sanitaria La Paz, Madrid 28029, Spain
    Free Radic Biol Med 52:473-87. 2012
    ..The stability of Nrf2 involves the interaction of two degradation domains, designated Neh2 and Neh6, with the E3 ubiquitin ligase adaptors, Keap1 and ?-TrCP, respectively...
  24. ncbi Peptide inhibitors of the Keap1-Nrf2 protein-protein interaction
    Rowena Hancock
    Department of Pharmaceutical and Biological Chemistry, School of Pharmacy, London WC1N 1AX, UK
    Free Radic Biol Med 52:444-51. 2012
    ..We describe the structure-activity relationships for a series of peptides based upon regions of the Nrf2 Neh2 domain, of varying length and sequence, that interact with the Keap1 Kelch domain and disrupt the interaction with ..
  25. ncbi DNA base excision repair gene polymorphisms modulate human cognitive performance and decline during normal life span
    Meryl S Lillenes
    Centre for Molecular Biology and Neuroscience, Institute of Microbiology, University of Oslo, Norway
    Mech Ageing Dev 132:449-58. 2011
    ..MutYH(His324Gln), APE1(Gln51His), APE1(Glu148Asp), XRCC1(Lys298Asn), XRCC1(Arg7Leu), NEIL1(Asp252Asn), and NEIL2(Arg257Leu). XRCC1(Arg7Leu) and PolB(Pro242Arg) were characterized by single nucleotide variations (?0...
  26. ncbi Development of Neh2-luciferase reporter and its application for high throughput screening and real-time monitoring of Nrf2 activators
    Natalya A Smirnova
    Burke Medical Research Institute, Department of Neurology and Neuroscience, Weill Medical College of Cornell University, White Plains, NY 10605, USA
    Chem Biol 18:752-65. 2011
    ..To directly monitor stabilization of Nrf2, we fused its Neh2 domain, responsible for the interaction with its nucleocytoplasmic regulator, Keap1, to firefly luciferase (Neh2-..
  27. ncbi Eukaryotic endonuclease VIII-like proteins: new components of the base excision DNA repair system
    I R Grin
    Institute of Chemical Biology and Fundamental Medicine, Siberian Division of the Russian Academy of Sciences, Novosibirsk, Russia
    Biochemistry (Mosc) 76:80-93. 2011
    ..In 2002, three new human DNA glycosylases (NEIL1, NEIL2, and NEIL3) were discovered, all homologous to endonuclease VIII, a bacterial protein, which also participates in ..
  28. ncbi Duffy-null-associated low neutrophil counts influence HIV-1 susceptibility in high-risk South African black women
    Veron Ramsuran
    HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa
    Clin Infect Dis 52:1248-56. 2011
    ..The influence of pre-seroconversion levels of peripheral blood cell counts (PBCs) on the risk of acquiring human immunodeficiency virus (HIV)-1 infection among Africans is unknown...
  29. ncbi Integrative analysis of array-comparative genomic hybridisation and matched gene expression profiling data reveals novel genes with prognostic significance in oesophageal adenocarcinoma
    X Y Goh
    MRC Cancer Cell Unit, Hutchison MRC Research Centre, Cambridge, UK
    Gut 60:1317-26. 2011
    ..This study aimed to use genome-wide genomic and expression data to enhance the understanding of OAC pathogenesis and identify groups with differential outcomes...
  30. ncbi Molecular mechanisms of the Keap1–Nrf2 pathway in stress response and cancer evolution
    Keiko Taguchi
    Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, 2 1 Seiryo cho, Aoba ku, Sendai 980 8575, Japan
    Genes Cells 16:123-40. 2011
    ..in which one molecule of Nrf2 associates with two molecules of Keap1 by using two binding sites within the Neh2 domain of Nrf2. This two-site binding appears critical for Nrf2 ubiquitination...
  31. ncbi Induction of NEIL1 and NEIL2 DNA glycosylases in aniline-induced splenic toxicity
    Huaxian Ma
    Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA
    Toxicol Appl Pharmacol 251:1-7. 2011
    ..of NEIL1/2 was assayed using a bubble structure substrate containing 5-OHU (preferred substrates for NEIL1 and NEIL2) and by quantitating the cleavage products. Aniline treatment led to a 1...
  32. ncbi Specific Inhibition of NEIL-initiated repair of oxidized base damage in human genome by copper and iron: potential etiological linkage to neurodegenerative diseases
    Muralidhar L Hegde
    Department of Biochemistry, University of Texas Medical Branch, Galveston, Texas 77555, USA
    J Biol Chem 285:28812-25. 2010
    ..repair pathway, initiated with one of four major DNA glycosylases: NTH1 or OGG1 (of the Nth family) or NEIL1 or NEIL2 (of the Nei family)...
  33. ncbi The mouse ortholog of NEIL3 is a functional DNA glycosylase in vitro and in vivo
    Minmin Liu
    Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Stafford Hall, 95 Carrigan Drive, Burlington, VT 05405 0086, USA
    Proc Natl Acad Sci U S A 107:4925-30. 2010
    ..have been identified in mammals that are homologous to the Escherichia coli Fpg and Nei proteins, Neil1, Neil2, and Neil3...
  34. ncbi Inactivation of NEIL2 DNA glycosylase by pyridoxal phosphate reveals a loop important for substrate binding
    Inga R Grin
    SB RAS Institute of Chemical Biology and Fundamental Medicine, 8 Lavrentieva Ave, Novosibirsk 630090, Russia
    Biochem Biophys Res Commun 394:100-5. 2010
    ..Of six enzymes tested, only endonuclease VIII-like protein 2 (NEIL2) was significantly inhibited by PLP. The inhibition was due to Schiff base formation between PLP and the enzyme...
  35. ncbi Hepatitis C virus induces oxidative stress, DNA damage and modulates the DNA repair enzyme NEIL1
    Sampa Pal
    Department of Laboratory Medicine, University of Washington, Seattle, Washington 98195 7110 USA
    J Gastroenterol Hepatol 25:627-34. 2010
    ..In the current study we examined the induction of reactive oxygen species (ROS) resulting from HCV infection and evaluated its effect on the host DNA damage and repair machinery...
  36. ncbi Regulatory regions responsive to oxidative stress in the promoter of the human DNA glycosylase gene NEIL2
    Carla J Kinslow
    Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX 77555 1062, USA
    Mutagenesis 25:171-7. 2010
    ..If not repaired, these lesions could lead to genomic instability and, potentially, to cancer development. NEIL2 (EC 4.2.99...
  37. ncbi REG4, NEIL2, and BIRC5 gene expression correlates with gamma-radiation sensitivity in patients with rectal cancer receiving radiotherapy
    Takashi Kobunai
    Department of Surgery, Teikyo University School of Medicine, 2 11 1 Kaga, Itabashi ku, Tokyo 173 8605, Japan
    Anticancer Res 31:4147-53. 2011
    ..The present study aimed to identify genes that influence the susceptibility of cancer cells to radiation...
  38. ncbi Interaction of the human DNA glycosylase NEIL1 with proliferating cell nuclear antigen. The potential for replication-associated repair of oxidized bases in mammalian genomes
    Hong Dou
    Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555 1079, USA
    J Biol Chem 283:3130-40. 2008
    NEIL1 and NEIL2 compose a family of DNA glycosylases that is distinct from that of the other two DNA glycosylases, OGG1 and NTH1, all of which are involved in repair of oxidized bases in mammalian genomes...
  39. ncbi Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex
    Donna D Zhang
    Department of Biochemistry, University of Missouri Columbia, M121 Medical Sciences Building, Columbia, MO 65212, USA
    Mol Cell Biol 24:10941-53. 2004
    ..E3 ubiquitin ligase complex with Cul3 and Rbx1 that targets multiple lysine residues located in the N-terminal Neh2 domain of Nrf2 for ubiquitin conjugation both in vivo and in vitro...
  40. ncbi Recognition of the oxidized lesions spiroiminodihydantoin and guanidinohydantoin in DNA by the mammalian base excision repair glycosylases NEIL1 and NEIL2
    M Katie Hailer
    Department of Chemistry, The University of Montana, Missoula, MT 59812, USA
    DNA Repair (Amst) 4:41-50. 2005
    ..Herein we report that two recently identified mammalian glycosylases, NEIL1 and NEIL2, showed a high affinity for recognition and cleavage of DNA containing Gh/Ia and Sp lesions...
  41. ncbi Identification of a zinc finger domain in the human NEIL2 (Nei-like-2) protein
    Aditi Das
    Sealy Center for Molecular Science and Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, Texas 77555 1079, USA
    J Biol Chem 279:47132-8. 2004
    The recently identified human NEIL2 (Nei-like-2) protein, a DNA glycosylase/AP lyase specific for oxidatively damaged bases, shares structural features and reaction mechanism with the Escherichia coli DNA glycosylases, Nei and Fpg...
  42. ncbi Redox-regulated turnover of Nrf2 is determined by at least two separate protein domains, the redox-sensitive Neh2 degron and the redox-insensitive Neh6 degron
    Michael McMahon
    Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom
    J Biol Chem 279:31556-67. 2004
    ..In homeostatic COS1 cells, the Neh2 degron confers on Nrf2 a half-life of less than 10 min...
  43. ncbi Differential specificity of human and Escherichia coli endonuclease III and VIII homologues for oxidative base lesions
    Atsushi Katafuchi
    Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Higashi Hiroshima 739 8526, Japan
    J Biol Chem 279:14464-71. 2004
    ..However, detailed analysis of the cellular activity suggests that hNEIL1 has a significant role in the repair of 5S-Tg in human cells...
  44. ncbi Repair of oxidized bases in DNA bubble structures by human DNA glycosylases NEIL1 and NEIL2
    Hong Dou
    Sealy Center for Molecular Science and Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, Texas 77555, USA
    J Biol Chem 278:49679-84. 2003
    ..The newly discovered human DNA glycosylases, NEIL1 and NEIL2, are distinct in structural features and reaction mechanism from the previously characterized NTH1 and OGG1 but ..
  45. ncbi Phosphorylation of Nrf2 at Ser40 by protein kinase C in response to antioxidants leads to the release of Nrf2 from INrf2, but is not required for Nrf2 stabilization/accumulation in the nucleus and transcriptional activation of antioxidant response element
    David A Bloom
    Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 278:44675-82. 2003
    ..The PKC site at Ser40 is conserved among species and lies in the Neh2 domain, which interacts with INrf2...
  46. ncbi The novel DNA glycosylase, NEIL1, protects mammalian cells from radiation-mediated cell death
    Thomas A Rosenquist
    Department of Pharmacological Sciences, SUNY Stony Brook, Stony Brook, NY 11794, USA
    DNA Repair (Amst) 2:581-91. 2003
    ..Three human genes, designated NEIL1, NEIL2 and NEIL3, encode proteins that contain sequence homologies to Nei and Fpg...
  47. ncbi Keap1-dependent proteasomal degradation of transcription factor Nrf2 contributes to the negative regulation of antioxidant response element-driven gene expression
    Michael McMahon
    Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom
    J Biol Chem 278:21592-600. 2003
    ..Within Nrf2, the N-terminal Neh2 domain is identified as the redox-sensitive degron...
  48. ncbi A novel human DNA glycosylase that removes oxidative DNA damage and is homologous to Escherichia coli endonuclease VIII
    Viswanath Bandaru
    Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, The University of Vermont, Stafford Hall, 95 Carrigan Drive, Burlington, VT 05405 0068, USA
    DNA Repair (Amst) 1:517-29. 2002
    ..Furthermore, inactivation of active site residues shown to be important in Escherichia coli Nei inactivate the human enzyme. The hNEI1 gene is located on the long arm of chromosome 15 that is frequently deleted in human cancers...
  49. ncbi A back-up glycosylase in Nth1 knock-out mice is a functional Nei (endonuclease VIII) homologue
    Masashi Takao
    Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980 8575, Japan
    J Biol Chem 277:42205-13. 2002
    ..These results suggest that NEIL1 is a back-up glycosylase for NTH1 with unique substrate specificity and tissue-specific expression...
  50. ncbi Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants
    Albena T Dinkova-Kostova
    The Lewis B and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 99:11908-13. 2002
    ..and purified murine Keap1 and demonstrated on native gels the formation of complexes of Keap1 with the Neh2 domain of Nrf2 and their concentration-dependent disruption by inducers such as sulforaphane and bis(2-..
  51. ncbi Identification and characterization of a novel human DNA glycosylase for repair of cytosine-derived lesions
    Tapas K Hazra
    Department of Human Biological Chemistry and Genetics, Sealy Center for Molecular Science, University of Texas Medical Branch, 6 136 Medical Research Building, Rte 1079, Galveston, TX 77555, USA
    J Biol Chem 277:30417-20. 2002
    ..A. 99, 3523-3528). Here we report characterization of the second protein, originally named NEH2 and now renamed NEIL2 (Nei-like). The 37-kDa wild-type NEIL2 expressed in and purified from E...
  52. ncbi The murine DNA glycosylase NEIL2 (mNEIL2) and human DNA polymerase beta bind microtubules in situ and in vitro
    Kimberly A Conlon
    Department of Pharmacological Sciences, School of Medicine University Hospital and Medical Center, State University of New York Stony Brook, NY 11794 8651, USA
    DNA Repair (Amst) 4:419-31. 2005
    ....
  53. ncbi Modifying specific cysteines of the electrophile-sensing human Keap1 protein is insufficient to disrupt binding to the Nrf2 domain Neh2
    Aimee L Eggler
    Center for Pharmaceutical Biotechnology, University of Illinois, Chicago, IL 60607, USA
    Proc Natl Acad Sci U S A 102:10070-5. 2005
    ..Under basal conditions, Keap1 sequesters Nrf2 in the cytoplasm by binding to its Neh2 domain...
  54. ncbi Differential modulation of base excision repair activities during brain ontogeny: implications for repair of transcribed DNA
    Ella W Englander
    Department of Surgery, The University of Texas Medical Branch, Shriners Hospitals for Children, 815 Market Street, Galveston, TX 77550, USA
    Mech Ageing Dev 127:64-9. 2006
    ..While a subset of BER enzymes, exhibited declining expression and excision activities, expression of NEIL1 and NEIL2 glycosylases increased during brain development...
  55. ncbi Subcellular localization and cytoplasmic complex status of endogenous Keap1
    Yoriko Watai
    Graduate School of Comprehensive Human Sciences, Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Japan
    Genes Cells 12:1163-78. 2007
    ..an adaptor for Cullin-3-based ubiquitin ligase, and a regulator of Nrf2 activity through the interaction with Nrf2 Neh2 domain...
  56. ncbi Different electrostatic potentials define ETGE and DLG motifs as hinge and latch in oxidative stress response
    Kit I Tong
    Graduate School of Comprehensive Human Sciences, Center for TARA, JST ERATO Environmental Response Project, University of Tsukuba, 1 1 1 Tennoudai, Tsukuba 305 8577, Japan
    Mol Cell Biol 27:7511-21. 2007
    ..The DLG motif works to correctly position the lysines within the Nrf2 Neh2 domain for efficient ubiquitination...
  57. ncbi Novel vectors for homologous recombination strategies in mouse embryonic stem cells: an ES cell line expressing EGFP under control of the 5T4 promoter
    Flor M Perez Campo
    Stem Cell Biology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester, UK
    Exp Cell Res 313:3604-15. 2007
    ..As proof-of-principle, we have utilized the knock-out targeting vector to modify the NEIL2 locus in ES cells...
  58. ncbi Human non-synonymous single nucleotide polymorphisms can influence ubiquitin-mediated protein degradation
    Sevtap Savas
    Fred A Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    OMICS 11:200-8. 2007
    ..in the presence of nsSNPs in CCND3, PMS2, POLE4, SITPEC, and PPARG and putative PEST motifs were created in NEIL2, BIRC4, MLL2, and PPP1R15A...
  59. ncbi Human polymorphic variants of the NEIL1 DNA glycosylase
    Laura M Roy
    Center for Research on Occupational and Environmental Toxicology, Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon 97239 3098, USA
    J Biol Chem 282:15790-8. 2007
    ..reactive oxygen species is primarily initiated by a series of DNA glycosylases that include OGG1, NTH1, NEIL1, and NEIL2. To explore the functional significance of NEIL1, we recently reported that neil1 knock-out and heterozygotic mice ..
  60. ncbi Different organization of base excision repair of uracil in DNA in nuclei and mitochondria and selective upregulation of mitochondrial uracil-DNA glycosylase after oxidative stress
    M Akbari
    Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, N 7006 Trondheim, Norway
    Neuroscience 145:1201-12. 2007
    ..The DNA glycosylases Nei-like DNA glycosylase 1 (NEIL1), Nei-like DNA glycosylase 2 (NEIL2), mitochondrial uracil-DNA glycosylase 1 (UNG1), nuclear uracil-DNA glycosylase 2 (UNG2) and endonuclease III-like ..
  61. ncbi Evaluation of NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 genes in familial colorectal cancer predisposition
    Peter Broderick
    Section of Cancer Genetics, Brookes Lawley Building, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK
    BMC Cancer 6:243. 2006
    ..It is conceivable that germline sequence variation in other BER pathway genes such as NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 also contribute to CRC susceptibility.
  62. ncbi NEIL2-initiated, APE-independent repair of oxidized bases in DNA: Evidence for a repair complex in human cells
    Aditi Das
    Department of Biochemistry and Molecular Biology, Sealy Center for Molecular Science, University of Texas Medical Branch, 6 136 Medical Research Building, Route 1079, Galveston, TX 77555, USA
    DNA Repair (Amst) 5:1439-48. 2006
    ..barely active in removing 3' phosphate generated by the recently discovered mammalian DNA glycosylases NEIL1 and NEIL2. We showed earlier that the 3' phosphate generated by NEIL1 is efficiently removed by polynucleotide kinase (PNK) ..
  63. ncbi Deoxyribophosphate lyase activity of mammalian endonuclease VIII-like proteins
    Inga R Grin
    SB RAS Institute of Chemical Biology and Fundamental Medicine, Novosibirsk 630090, Russia
    FEBS Lett 580:4916-22. 2006
    ..Here, we demonstrate that NEIL1 and NEIL2, mammalian homologs of bacterial endonuclease VIII, excise dRP by beta-elimination with the efficiency similar to ..
  64. ncbi Negative regulation of the Nrf1 transcription factor by its N-terminal domain is independent of Keap1: Nrf1, but not Nrf2, is targeted to the endoplasmic reticulum
    Yiguo Zhang
    Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK
    Biochem J 399:373-85. 2006
    ..Within acidic domain 1, residues 156-242 share 43% identity with the Neh2 (Nrf2-ECH homology 2) degron of Nrf2 that serves to destabilize this latter transcription factor through an ..
  65. ncbi Dimerization of substrate adaptors can facilitate cullin-mediated ubiquitylation of proteins by a "tethering" mechanism: a two-site interaction model for the Nrf2-Keap1 complex
    Michael McMahon
    Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom
    J Biol Chem 281:24756-68. 2006
    ..facilitates ubiquitylation of the Nrf2 transcription factor but only when this substrate possesses within its Neh2 domain a second cryptic Keap1-binding site, the DLG motif, in addition to its previously described ETGE site...
  66. ncbi Keap1 recruits Neh2 through binding to ETGE and DLG motifs: characterization of the two-site molecular recognition model
    Kit I Tong
    Graduate School of Life and Environmental Sciences, University of Tsukuba, 1 1 1 Tennoudai, Tsukuba 305 8572, Japan
    Mol Cell Biol 26:2887-900. 2006
    ..We found that the Neh2 domain of Nrf2 is an intrinsically disordered but biologically active regulatory domain containing a 33-residue ..
  67. ncbi Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain
    K Itoh
    Center for Tsukuba Advanced Research Alliance and Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba 305 8577, Japan
    Genes Dev 13:76-86. 1999
    ..The activation of Nrf2 leads in turn to the induction of phase II enzyme and antioxidative stress genes in response to electrophiles and reactive oxygen species...
  68. ncbi Inherited predisposition to colorectal adenomas caused by multiple rare alleles of MUTYH but not OGG1, NUDT1, NTH1 or NEIL 1, 2 or 3
    A R Dallosso
    Institute of Medical Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK
    Gut 57:1252-5. 2008
    ..MUTYH functions in the DNA base excision repair pathway and has a key role in the repair of oxidative DNA damage...

Research Grants31

  1. Repair of Oxidized Bases in Mammalian Genomes
    Sankar Mitra; Fiscal Year: 2010
    ..In our previous project period we characterized human glycosylases (NEIL1 and NEIL2) with overlapping substrate preferences as OGG1 and NTH1...
  2. Repair of Oxidized Bases in Mammalian Genomes
    Sankar Mitra; Fiscal Year: 2007
    ..In our previous project period we characterized human glycosylases (NEIL1 and NEIL2) with overlapping substrate preferences as OGG1 and NTH1...
  3. Repair of Oxidized Bases in Mammalian Genomes
    Sankar Mitra; Fiscal Year: 2009
    ..In our previous project period we characterized human glycosylases (NEIL1 and NEIL2) with overlapping substrate preferences as OGG1 and NTH1...
  4. Repair of Oxidized Bases in Mammalian Genomes
    Sankar Mitra; Fiscal Year: 2010
    ..In our previous project period we characterized human glycosylases (NEIL1 and NEIL2) with overlapping substrate preferences as OGG1 and NTH1...
  5. Regulation of Nrf2 Signaling
    Michael Freeman; Fiscal Year: 2009
    ..Aim 2 will determine if key Keap1 Cys residues regulate association between the Neh2 domain of Nrf2 and Keap1 following reaction with thiol-reactive electrophiles...
  6. Mechanisms of Neurotoxicity of Combustion-smoke Inhalation to the Brain
    Ella W Englander; Fiscal Year: 2010
    ..abstract_text> ..
  7. HYPOXIA-INDUCED DNA DAMAGE AND REPAIR IN THE RAT BRAIN
    Ella Englander; Fiscal Year: 2009
    ..abstract_text> ..
  8. HYPOXIA-INDUCED DNA DAMAGE AND REPAIR IN THE RAT BRAIN
    Ella W Englander; Fiscal Year: 2010
    ..abstract_text> ..
  9. Repair of oxidative damage in mammalian genomes
    Tapas K Hazra; Fiscal Year: 2010
    ..b>NEIL2 has a 4- to 5-fold higher affinity and activity for 5-OHU in bubble vs duplex DNA, and it excises 8-oxoG from ..
  10. Repair of oxidative damage in mammalian genomes
    TAPAS HAZRA; Fiscal Year: 2009
    ..b>NEIL2 has a 4- to 5-fold higher affinity and activity for 5-OHU in bubble vs duplex DNA, and it excises 8-oxoG from ..
  11. HYPOXIA-INDUCED DNA DAMAGE AND REPAIR IN THE BRAIN
    Ella Englander; Fiscal Year: 2004
    ..This information will augment strategies seeking to reduce neuropathologies of brain hypoxia in humans. ..
  12. MAMMALIAN OXIDATIVE DNA DAMAGE REPAIR
    Thomas Rosenquist; Fiscal Year: 2004
    ..The effects of altering the level of ogg1 gene expression on the rate of mutagenesis and tumorigenesis also will be determined. ..
  13. HYPOXIA-INDUCED DNA DAMAGE AND REPAIR IN THE RAT BRAIN
    Ella Englander; Fiscal Year: 2007
    ....
  14. Repair of oxidative damage in mammalian genomes
    TAPAS HAZRA; Fiscal Year: 2007
    ..b>NEIL2 has a 4- to 5-fold higher affinity and activity for 5-OHU in bubble vs duplex DNA, and it excises 8-oxoG from ..
  15. Mechanisms of Neurotoxicity of Combustion-smoke Inhalation to the Brain
    Ella Englander; Fiscal Year: 2007
    ....