dna glycosylases

Summary

Summary: A family of DNA repair enzymes that recognize damaged nucleotide bases and remove them by hydrolyzing the N-glycosidic bond that attaches them to the sugar backbone of the DNA molecule. The process called BASE EXCISION REPAIR can be completed by a DNA-(APURINIC OR APYRIMIDINIC SITE) LYASE which excises the remaining RIBOSE sugar from the DNA.

Top Publications

  1. doi DNA repair in mammalian cells: Base excision repair: the long and short of it
    A B Robertson
    Centre for Molecular Biology and Neuroscience, Rikshospitalet HF, University of Oslo, Oslo, Norway
    Cell Mol Life Sci 66:981-93. 2009
  2. pmc A base-excision DNA-repair protein finds intrahelical lesion bases by fast sliding in contact with DNA
    Paul C Blainey
    Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
    Proc Natl Acad Sci U S A 103:5752-7. 2006
  3. pmc Base excision repair and lesion-dependent subpathways for repair of oxidative DNA damage
    David Svilar
    Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    Antioxid Redox Signal 14:2491-507. 2011
  4. pmc Detection of damaged DNA bases by DNA glycosylase enzymes
    Joshua I Friedman
    Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, WBSB 314, 725 North Wolfe Street, Baltimore, Maryland 21205, USA
    Biochemistry 49:4957-67. 2010
  5. ncbi DEMETER, a DNA glycosylase domain protein, is required for endosperm gene imprinting and seed viability in arabidopsis
    Yeonhee Choi
    Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, CA 94720, USA
    Cell 110:33-42. 2002
  6. ncbi Genetic polymorphisms in the base excision repair pathway and cancer risk: a HuGE review
    Rayjean J Hung
    Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France
    Am J Epidemiol 162:925-42. 2005
  7. pmc Dimerization and opposite base-dependent catalytic impairment of polymorphic S326C OGG1 glycosylase
    Jeff W Hill
    Laboratory of Cellular and Molecular Biology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224 6825, USA
    Nucleic Acids Res 34:1620-32. 2006
  8. pmc Poly (ADP-ribose) polymerase (PARP) is not involved in base excision repair but PARP inhibition traps a single-strand intermediate
    Cecilia E Ström
    Department of Genetics, Microbiology and Toxicology, Stockholm University, S 106 91 Stockholm, Sweden
    Nucleic Acids Res 39:3166-75. 2011
  9. pmc DNA demethylation in the Arabidopsis genome
    Jon Penterman
    Department of Plant and Microbial Biology, University of California, Berkeley, CA 94720, USA
    Proc Natl Acad Sci U S A 104:6752-7. 2007
  10. doi Contribution of the TP53, OGG1, CHRNA3, and HLA-DQA1 genes to the risk for lung squamous cell carcinoma
    Takashi Kohno
    Biology Division, National Cancer Center Research Institute Division of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan
    J Thorac Oncol 6:813-7. 2011

Detail Information

Publications414 found, 100 shown here

  1. doi DNA repair in mammalian cells: Base excision repair: the long and short of it
    A B Robertson
    Centre for Molecular Biology and Neuroscience, Rikshospitalet HF, University of Oslo, Oslo, Norway
    Cell Mol Life Sci 66:981-93. 2009
    ..The BER pathway is initiated by one of many DNA glycosylases, which recognize and catalyze the removal of damaged bases...
  2. pmc A base-excision DNA-repair protein finds intrahelical lesion bases by fast sliding in contact with DNA
    Paul C Blainey
    Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
    Proc Natl Acad Sci U S A 103:5752-7. 2006
    ..5 kcal/mol (1 kcal = 4.2 kJ). This nearly barrierless Brownian sliding indicates that DNA glycosylases locate lesion bases by a massively redundant search in which the enzyme selectively binds 8-oxoguanine under ..
  3. pmc Base excision repair and lesion-dependent subpathways for repair of oxidative DNA damage
    David Svilar
    Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    Antioxid Redox Signal 14:2491-507. 2011
    ..We discuss the multiple BER subpathways that are initiated by one of 11 different DNA glycosylases of three subtypes: (a) bifunctional with an associated β-lyase activity; (b) monofunctional; and (c) ..
  4. pmc Detection of damaged DNA bases by DNA glycosylase enzymes
    Joshua I Friedman
    Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, WBSB 314, 725 North Wolfe Street, Baltimore, Maryland 21205, USA
    Biochemistry 49:4957-67. 2010
    ....
  5. ncbi DEMETER, a DNA glycosylase domain protein, is required for endosperm gene imprinting and seed viability in arabidopsis
    Yeonhee Choi
    Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, CA 94720, USA
    Cell 110:33-42. 2002
    ..In leaf, ectopic DME expression induces MEA and nicks the MEA promoter. Thus, a DNA glycosylase activates maternal expression of an imprinted gene in the central cell...
  6. ncbi Genetic polymorphisms in the base excision repair pathway and cancer risk: a HuGE review
    Rayjean J Hung
    Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France
    Am J Epidemiol 162:925-42. 2005
    ..Recommendations for future studies include pooling of individual data to facilitate evaluation of multigenic effects and detailed analysis of effect modification by environmental exposure...
  7. pmc Dimerization and opposite base-dependent catalytic impairment of polymorphic S326C OGG1 glycosylase
    Jeff W Hill
    Laboratory of Cellular and Molecular Biology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224 6825, USA
    Nucleic Acids Res 34:1620-32. 2006
    ..The altered substrate specificity, lack of stimulation by AP-endonuclease 1 (APE1) and anomalous DNA binding conformation of S326C OGG1 may contribute to its linkage to cancer incidence...
  8. pmc Poly (ADP-ribose) polymerase (PARP) is not involved in base excision repair but PARP inhibition traps a single-strand intermediate
    Cecilia E Ström
    Department of Genetics, Microbiology and Toxicology, Stockholm University, S 106 91 Stockholm, Sweden
    Nucleic Acids Res 39:3166-75. 2011
    ..Unexpectedly, addition of PARP inhibitor 2 h after DMS treatment still increased SSB levels indicating ongoing repair even at this late time point...
  9. pmc DNA demethylation in the Arabidopsis genome
    Jon Penterman
    Department of Plant and Microbial Biology, University of California, Berkeley, CA 94720, USA
    Proc Natl Acad Sci U S A 104:6752-7. 2007
    ..In Arabidopsis thaliana, DNA glycosylases of the DEMETER (DME) family remove methylcytosines from DNA...
  10. doi Contribution of the TP53, OGG1, CHRNA3, and HLA-DQA1 genes to the risk for lung squamous cell carcinoma
    Takashi Kohno
    Biology Division, National Cancer Center Research Institute Division of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan
    J Thorac Oncol 6:813-7. 2011
    ..Therefore, significance of these functional polymorphisms was evaluated in a population, in which polymorphisms in the GWAS genes showed associations with lung SQC risk...
  11. pmc Base-excision repair of oxidative DNA damage
    Sheila S David
    Department of Chemistry, University of California at Davis, 1 Shields Avenue, Davis, California 95616, USA
    Nature 447:941-50. 2007
    ..Recent structural studies have shown that 8-oxoguanine DNA glycosylases use an intricate series of steps to locate and excise 8-oxoguanine lesions efficiently against a high ..
  12. ncbi Repair and genetic consequences of endogenous DNA base damage in mammalian cells
    Deborah E Barnes
    Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
    Annu Rev Genet 38:445-76. 2004
    ..The genetic instability characteristic of cancer cells may be due, in part, to mutations in genes whose products normally function to ensure DNA integrity...
  13. pmc HIV-1 Vpr loads uracil DNA glycosylase-2 onto DCAF1, a substrate recognition subunit of a cullin 4A-ring E3 ubiquitin ligase for proteasome-dependent degradation
    Jinwoo Ahn
    Department of Structural Biology, University of Pittsburgh School of Medicine and Cancer Institute, Pittsburgh, Pennsylvania 15260, USA
    J Biol Chem 285:37333-41. 2010
    ..Taken together, our results show that the CRL4(DCAF1) E3 ubiquitin ligase can be subverted by Vpr to target UNG2 for degradation...
  14. 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
    ..That NEIL1/PNK could also repair the products of other DNA glycosylases suggests a broad role for this APE-independent BER pathway in mammals.
  15. pmc Recognition and processing of a new repertoire of DNA substrates by human 3-methyladenine DNA glycosylase (AAG)
    Chun Yue I Lee
    Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Biochemistry 48:1850-61. 2009
    ....
  16. pmc Active DNA demethylation mediated by DNA glycosylases
    Jian Kang Zhu
    Institute for Integrative Genome Biology and Department of Botany and Plant Sciences, University of California, Riverside, CA 92521, USA
    Annu Rev Genet 43:143-66. 2009
    ..Recent genetic and biochemical studies in Arabidopsis have demonstrated that a subfamily of DNA glycosylases function to promote DNA demethylation through a base excision-repair pathway...
  17. ncbi ROS1, a repressor of transcriptional gene silencing in Arabidopsis, encodes a DNA glycosylase/lyase
    Zhizhong Gong
    Departamento de Genetica, Universidad de Cordoba, 14071, Cordoba, Spain
    Cell 111:803-14. 2002
    ..We suggest that ROS1 is a DNA repair protein that represses homology-dependent transcriptional gene silencing by demethylating the target promoter DNA...
  18. ncbi Identification of genetic variants in base excision repair pathway and their associations with risk of esophageal squamous cell carcinoma
    Bingtao Hao
    Laboratory of Systems Biology, Beijing Institute of Radiation Medicine, Beijing, People s Republic of China
    Cancer Res 64:4378-84. 2004
    ..The results suggest that the polymorphisms in five BER genes may be associated with the susceptibility to ESCC in a Chinese population...
  19. ncbi An evolutionary analysis of the helix-hairpin-helix superfamily of DNA repair glycosylases
    Dee R Denver
    Department of Biology, Indiana University, USA
    Mol Biol Evol 20:1603-11. 2003
    The helix-hairpin-helix (HhH) superfamily of base excision repair DNA glycosylases is composed of multiple phylogenetically diverse enzymes that are capable of excising varying spectra of oxidatively and methyl-damaged bases...
  20. doi Arabidopsis DEMETER-LIKE proteins DML2 and DML3 are required for appropriate distribution of DNA methylation marks
    Ana Pilar Ortega-Galisteo
    Departamento de Genetica, Universidad de Cordoba, Edificio Gregor Mendel, Campus de Rabanales s n, 14071, Cordoba, Spain
    Plant Mol Biol 67:671-81. 2008
    ..We have found that DML2 and DML3 are 5-methylcytosine DNA glycosylases that are expressed in a wide range of plant organs...
  21. pmc HO* radicals induce an unexpected high proportion of tandem base lesions refractory to repair by DNA glycosylases
    Francois Bergeron
    Commissariat a l Energie Atomique, Institut Nanosciences et Cryogenie, Lésions des Acides Nucléiques, F 38054 Grenoble Cedex 9, France
    Proc Natl Acad Sci U S A 107:5528-33. 2010
    ..Interestingly, we show that >40% of the 8-oxodGuo involved in tandem lesions is refractory to excision by DNA glycosylases. Altogether our results demonstrate that, subsequently to a single oxidation event, peroxidation reactions ..
  22. ncbi Structure of a repair enzyme interrogating undamaged DNA elucidates recognition of damaged DNA
    Anirban Banerjee
    Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA
    Nature 434:612-8. 2005
    ..The structure reveals a remarkably effective gate-keeping strategy for lesion discrimination and suggests a mechanism for oxoG insertion into the hOGG1 active site...
  23. pmc Neil3 and NEIL1 DNA glycosylases remove oxidative damages from quadruplex DNA and exhibit preferences for lesions in the telomeric sequence context
    Jia Zhou
    From the Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, The University of Vermont, Burlington, Vermont 05405 0068 and
    J Biol Chem 288:27263-72. 2013
    ..We have tested the base excision activities of five mammalian DNA glycosylases (NEIL1, NEIL2, mNeil3, NTH1, and OGG1) on these lesion-containing quadruplex substrates and found that only ..
  24. 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
    ..Despite the absence of a putative nuclear localization signal, NEIL2 was predominantly localized in the nucleus. These results suggest that NEIL2 is involved in global genome repair mainly for removing oxidative products of cytosine...
  25. pmc HIV-1 Vpr function is mediated by interaction with the damage-specific DNA-binding protein DDB1
    Bärbel Schröfelbauer
    Infectious Disease Laboratory, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037 1099, USA
    Proc Natl Acad Sci U S A 104:4130-5. 2007
    ..In addition, Vpr causes rapid degradation of the uracil-DNA glycosylases UNG2 and SMUG1...
  26. pmc Uracil in DNA and its processing by different DNA glycosylases
    Torkild Visnes
    Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7489 Trondheim, Norway
    Philos Trans R Soc Lond B Biol Sci 364:563-8. 2009
    ..Five mammalian uracil-DNA glycosylases have been identified; these are mitochondrial UNG1 and nuclear UNG2, both encoded by the UNG gene, and the ..
  27. ncbi Uracil in DNA--occurrence, consequences and repair
    Hans E Krokan
    Institute of Cancer Research and Molecular Biology, Norwegian University of Science and Technology, N 7489 Trondheim, Norway
    Oncogene 21:8935-48. 2002
    ..At least four different human DNA glycosylases may remove uracil and thus generate an abasic site, which is itself cytotoxic and potentially mutagenic...
  28. pmc hMYH cell cycle-dependent expression, subcellular localization and association with replication foci: evidence suggesting replication-coupled repair of adenine:8-oxoguanine mispairs
    I Boldogh
    Department of Microbiology, Sealy Center for Environmental Health and Medicine, University of Texas Medical Branch, Galveston, TX 77555-1071 USA
    Nucleic Acids Res 29:2802-9. 2001
    ..The cell cycle-dependent expression and localization of hMYH at sites of DNA replication suggest a role for this glycosylase in immediate post-replication DNA base excision repair...
  29. pmc A structural hinge in eukaryotic MutY homologues mediates catalytic activity and Rad9-Rad1-Hus1 checkpoint complex interactions
    Paz J Luncsford
    Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 North Greene Street, Baltimore, MD 21201, USA
    J Mol Biol 403:351-70. 2010
    ..Thus, preserving the MYH/9-1-1 interaction contributes significantly to minimizing the mutagenic potential of oxidative DNA damage...
  30. ncbi Human homolog of the MutY repair protein (hMYH) physically interacts with proteins involved in long patch DNA base excision repair
    A Parker
    Department of Biochemistry and Molecular Biology, The University of Maryland, Baltimore, Maryland 21201, USA
    J Biol Chem 276:5547-55. 2001
    ..The PCNA- and RPA-binding sites of hMYH are further confirmed by peptide and antibody titration. These results suggest that hMYH repair is a long patch base excision repair pathway...
  31. doi Targeted deletion of the genes encoding NTH1 and NEIL1 DNA N-glycosylases reveals the existence of novel carcinogenic oxidative damage to DNA
    Michael K Chan
    Department of Pathology and Cancer Institute, New York University School of Medicine, New York, NY, United States
    DNA Repair (Amst) 8:786-94. 2009
    ....
  32. pmc DNA bending and a flip-out mechanism for base excision by the helix-hairpin-helix DNA glycosylase, Escherichia coli AlkA
    T Hollis
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    EMBO J 19:758-66. 2000
    ..The structure of the AlkA-DNA complex offers the first glimpse of a helix-hairpin-helix (HhH) glycosylase complexed to DNA. Modeling studies suggest that other HhH glycosylases can bind to DNA in a similar manner...
  33. pmc N-methylpurine DNA glycosylase and DNA polymerase beta modulate BER inhibitor potentiation of glioma cells to temozolomide
    Jiang bo Tang
    Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    Neuro Oncol 13:471-86. 2011
    ....
  34. pmc Cell cycle-specific UNG2 phosphorylations regulate protein turnover, activity and association with RPA
    Lars Hagen
    Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
    EMBO J 27:51-61. 2008
    ..Our findings may aid further studies of how UNG2 initiates mutagenic rather than repair processing of activation-induced deaminase-generated uracil at Ig loci in B cells...
  35. pmc Polymorphisms in hOGG1 and XRCC1 and risk of prostate cancer: effects modified by plasma antioxidants
    Jianjun Zhang
    Department of Public Health, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    Urology 75:779-85. 2010
    ..Accumulating evidence indicates that oxidative stress plays a role in prostate carcinogenesis...
  36. doi The hOGG1 Ser326Cys polymorphism and breast cancer risk: a meta-analysis
    Weiguang Yuan
    Institute of Cancer Prevention and Treatment, Harbin Medical University, Baojian Road 6, Nangang District, 150081 Harbin, China
    Breast Cancer Res Treat 122:835-42. 2010
    ..The meta-analysis suggested that the hOGG1 326Cys allele plays a significant protective effect to breast cancer in European women...
  37. pmc A unified view of base excision repair: lesion-dependent protein complexes regulated by post-translational modification
    Karen H Almeida
    Department of Physical Sciences, Rhode Island College, 600 Mt Pleasant Avenue, Providence, RI 02908 1991, United States
    DNA Repair (Amst) 6:695-711. 2007
    ..In this review, we have summarized the reported BER protein-protein interactions and protein post-translational modifications and discuss the impact on DNA repair capacity and complex formation...
  38. ncbi Polymorphisms in base-excision repair and nucleotide-excision repair genes in relation to lung cancer risk
    Kim De Ruyck
    Department of Anatomy, Embryology, Histology and Medical Physics, Ghent University, Proeftuinstraat 86, B 9000 Gent, Belgium
    Mutat Res 631:101-10. 2007
    ..In conclusion, the APE1 Asp148Glu polymorphism is highly predictive for lung cancer, and cumulative cigarette smoking modifies the associations between the XRCC1 Arg399Gln and the XPD Lys751Gln polymorphisms and lung cancer risk...
  39. ncbi Nasopharyngeal carcinoma and genetic polymorphisms of DNA repair enzymes XRCC1 and hOGG1
    En Yu Cho
    Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei 10018, Taiwan
    Cancer Epidemiol Biomarkers Prev 12:1100-4. 2003
    ..5-177). Polymorphisms of the DNA repair genes hOGG1 (codon 326) and XRCC1 (codon 280) are associated with an altered risk of NPC. Carriers of multiple putative high-risk genotypes have the highest risk of developing NPC...
  40. pmc Cloning and characterization of hOGG1, a human homolog of the OGG1 gene of Saccharomyces cerevisiae
    J P Radicella
    Laboratoire de Radiobiologie du DNA, Commissariat a l Energie Atomique, Departement de Radiobiologie et Radiopathologie, UMR217 Centre National de la Recherche Scientifique, 92265 Fontenay aux Roses, France
    Proc Natl Acad Sci U S A 94:8010-5. 1997
    ....
  41. pmc Base excision repair initiation revealed by crystal structures and binding kinetics of human uracil-DNA glycosylase with DNA
    S S Parikh
    The Skaggs Institute for Chemical Biology, Department of Molecular Biology, MB 4, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 1027, USA
    EMBO J 17:5214-26. 1998
    ..Thus, AP site binding may couple damage-specific and damage-general steps of BER without requiring direct protein-protein interactions...
  42. pmc Identification of human MutY homolog (hMYH) as a repair enzyme for 2-hydroxyadenine in DNA and detection of multiple forms of hMYH located in nuclei and mitochondria
    T Ohtsubo
    Department of Biochemistry, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
    Nucleic Acids Res 28:1355-64. 2000
    ..These hMYH transcripts are likely to encode multiple authentic hMYH polypeptides including the 52, 53 and 57 kDa polypeptides detected in Jurkat cells...
  43. pmc Recent advances in the structural mechanisms of DNA glycosylases
    Sonja C Brooks
    Department of Biological Sciences and Center for Structural Biology, Vanderbilt University, Nashville, TN 37232, USA
    Biochim Biophys Acta 1834:247-71. 2013
    b>DNA glycosylases safeguard the genome by locating and excising a diverse array of aberrant nucleobases created from oxidation, alkylation, and deamination of DNA...
  44. doi Structure-dependent DNA damage and repair in a trinucleotide repeat sequence
    Daniel A Jarem
    Department of Chemistry, Brown University, Providence, Rhode Island 02912, USA
    Biochemistry 48:6655-63. 2009
    ..These observed structure-dependent patterns of DNA damage and repair may contribute to the OGG1-dependent mechanism of trinucleotide repeat expansion...
  45. ncbi Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH
    Oliver M Sieber
    Molecular and Population Genetics Laboratory, London Research Institute, Cancer Research UK, London, United Kingdom
    N Engl J Med 348:791-9. 2003
    ..Tumors from affected persons displayed excess somatic transversions of a guanine-cytosine pair to a thymine-adenine pair (G:C-->T:A) in the APC gene...
  46. pmc Excision of hypoxanthine from DNA containing dIMP residues by the Escherichia coli, yeast, rat, and human alkylpurine DNA glycosylases
    M Saparbaev
    URA 147 Centre National de la Recherche Scientifique, Institut Gustave Roussy, Villejuif, France
    Proc Natl Acad Sci U S A 91:5873-7. 1994
    ..ANPG protein, APDG protein, and MAG protein--the 3-methyladenine DNA glycosylases of human, rat, and yeast origin, respectively--were also able to release hypoxanthine from various DNA ..
  47. ncbi Dissecting the broad substrate specificity of human 3-methyladenine-DNA glycosylase
    PATRICK J O'BRIEN
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 279:9750-7. 2004
    ..These findings suggest that AAG reconciles a broad substrate tolerance with the biological imperative to avoid normal DNA by excluding normal bases from the active site rather than by specifically recognizing each lesion...
  48. ncbi XRCC1 interactions with multiple DNA glycosylases: a model for its recruitment to base excision repair
    Anna Campalans
    Departement de Radiobiologie et Radiopathologie, CEA, UMR217 CNRS CEA, 18 route du Panorama, F 92265 Fontenay aux Roses, France
    DNA Repair (Amst) 4:826-35. 2005
    ..XRCC1 participates in the first step of BER by interacting with the human DNA glycosylases hOGG1 and NEIL1...
  49. pmc Targeted deletion of alkylpurine-DNA-N-glycosylase in mice eliminates repair of 1,N6-ethenoadenine and hypoxanthine but not of 3,N4-ethenocytosine or 8-oxoguanine
    B Hang
    Donner Laboratory, Lawrence Berkeley National Laboratory, University of California, 94720, USA
    Proc Natl Acad Sci U S A 94:12869-74. 1997
    ....
  50. ncbi Crystal structure of a G:T/U mismatch-specific DNA glycosylase: mismatch recognition by complementary-strand interactions
    T E Barrett
    Department of Biochemistry and Molecular Biology, University College London, United Kingdom
    Cell 92:117-29. 1998
    ..Details of the MUG structure explain its thymine DNA-glycosylase activity and the specificity for G:U/T mispairs, which derives from direct recognition of guanine on the complementary strand...
  51. pmc Cloning and expression in Escherichia coli of the OGG1 gene of Saccharomyces cerevisiae, which codes for a DNA glycosylase that excises 7,8-dihydro-8-oxoguanine and 2,6-diamino-4-hydroxy-5-N-methylformamidopyrimidine
    P A Van Der Kemp
    Unité de Recherche Associée 147 Centre National de la Recherche Scientifique, Villejuif, France
    Proc Natl Acad Sci U S A 93:5197-202. 1996
    ..The mechanism of strand cleavage by Ogg1 protein is probably due to the excision of 8-OxoG followed by a beta-elimination at the resulting apurinic/apyrimidinic site...
  52. pmc Nucleotide excision repair-initiating proteins bind to oxidative DNA lesions in vivo
    Hervé Menoni
    Department of Genetics, Erasmus MC, 3015 GE Rotterdam, Netherlands
    J Cell Biol 199:1037-46. 2012
    ....
  53. pmc Origin of endogenous DNA abasic sites in Saccharomyces cerevisiae
    Marie Guillet
    CEA, DSV, Departement de Radiobiologie et Radiopathologie, UMR 217 CNRS CEA Radiobiologie Moléculaire et Cellulaire, F 92265 Fontenay aux Roses, France
    Mol Cell Biol 23:8386-94. 2003
    ..In contrast, inactivation of the MAG1, OGG1, or NTG1 and NTG2 genes encoding DNA glycosylases involved in the repair of alkylation or oxidation damages does not suppress lethality...
  54. pmc DEMETER and REPRESSOR OF SILENCING 1 encode 5-methylcytosine DNA glycosylases
    Teresa Morales-Ruiz
    Departamento de Genetica, Universidad de Cordoba, 14071 Cordoba, Spain
    Proc Natl Acad Sci U S A 103:6853-8. 2006
    ..These findings suggest that a function of ROS1 and DME is to initiate erasure of 5-meC through a base excision repair process and provide strong biochemical evidence for the existence of an active DNA demethylation pathway in plants...
  55. ncbi The role of base excision repair in the sensitivity and resistance to temozolomide-mediated cell death
    Ram N Trivedi
    Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213 1863, USA
    Cancer Res 65:6394-400. 2005
    ..However, >80% of the DNA lesions induced by temozolomide are N-methylated bases that are recognized by DNA glycosylases and not by MGMT, and so resistance to temozolomide may also be due, in part, to robust base excision repair (..
  56. ncbi Human 3-methyladenine-DNA glycosylase: effect of sequence context on excision, association with PCNA, and stimulation by AP endonuclease
    Liqun Xia
    Biology Division, Beckman Research Institute, City of Hope National Medical Center, 1450 East Duarte Road, Duarte, CA 91010, USA
    J Mol Biol 346:1259-74. 2005
    ..Thus, PCNA could have a role in short-patch BER as well as in long-patch BER. Overall, the data reported here show how multiple factors contribute to the activity of MPG in cells...
  57. doi Inactivation by oxidation and recruitment into stress granules of hOGG1 but not APE1 in human cells exposed to sub-lethal concentrations of cadmium
    Anne Bravard
    CEA, Institut de Radiobiologie Cellulaire et Moleculaire, 18 route du Panorama, F 92265 Fontenay aux Roses, France
    Mutat Res 685:61-9. 2010
    ..In contrast to hOGG1, we show here that exposure to Cd does not affect the activity of the second enzyme of the pathway, the major AP endonuclease APE1...
  58. ncbi Recognition and removal of oxidized guanines in duplex DNA by the base excision repair enzymes hOGG1, yOGG1, and yOGG2
    Michael D Leipold
    Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, Utah 84112, USA
    Biochemistry 42:11373-81. 2003
    ..Indeed, the greater efficiency of the yOGG proteins for removal of the further oxidized products, Gh and Sp, over their 8-oxoguanine parent, suggests that these lesions may be the preferred substrates in vivo...
  59. doi Association of APE1 and hOGG1 polymorphisms with colorectal cancer risk in a Turkish population
    Emel Canbay
    Basaksehir State Hospital, Department of General Surgery, Basaksehir, Istanbul, Turkey
    Curr Med Res Opin 27:1295-302. 2011
    ..The aim of this study was to investigate the associations between the APE1 Asp148Glu, hOGG1 Ser326Cys, XRCC1 Arg399Gln, XRCC3 Thr241Met, XPD Lys751Gln, XPG Asp1104His polymorphisms and CRC risk in Turkish population...
  60. pmc Domain structure of the DEMETER 5-methylcytosine DNA glycosylase
    Young Geun Mok
    Department of Plant Science and Plant Genomics and Breeding Institute, Seoul National University, Seoul 151 921, Korea
    Proc Natl Acad Sci U S A 107:19225-30. 2010
    b>DNA glycosylases initiate the base excision repair (BER) pathway by excising damaged, mismatched, or otherwise modified bases...
  61. ncbi Structure of a DNA glycosylase searching for lesions
    Anirban Banerjee
    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA
    Science 311:1153-7. 2006
    b>DNA glycosylases must interrogate millions of base pairs of undamaged DNA in order to locate and then excise one damaged nucleobase. The nature of this search process remains poorly understood...
  62. ncbi Inherited variants of MYH associated with somatic G:C-->T:A mutations in colorectal tumors
    Nada Al-Tassan
    Institute of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN, UK
    Nat Genet 30:227-32. 2002
    ..Our findings link the inherited variants in MYH to the pattern of somatic APC mutation in family N and implicate defective base excision repair in predisposition to tumors in humans...
  63. pmc RNA editing changes the lesion specificity for the DNA repair enzyme NEIL1
    Jongchan Yeo
    Department of Chemistry, University of California, One Shields Avenue, Davis, CA 95616, USA
    Proc Natl Acad Sci U S A 107:20715-9. 2010
    ..As expected for an ADAR1 site, editing at this position is increased in human cells treated with interferon α. These results suggest a unique regulatory mechanism for DNA repair and extend our understanding of the impact of RNA editing...
  64. pmc Cell cycle regulation as a mechanism for functional separation of the apparently redundant uracil DNA glycosylases TDG and UNG2
    Ulrike Hardeland
    Centre for Biomedicine, DKBW, University of Basel, Mattenstrasse 28, CH 4058 Basel, Switzerland
    Nucleic Acids Res 35:3859-67. 2007
    ..Here, we report cell cycle regulation as a mechanism for the functional separation of apparently redundant DNA glycosylases. We show that cells entering S-phase eliminate TDG through the ubiquitin-proteasome system and then maintain ..
  65. pmc Transcriptional regulation of the base excision repair pathway by BRCA1
    Tapas Saha
    Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA
    J Biol Chem 285:19092-105. 2010
    ..These findings identify a novel mechanism through which BRCA1 may regulate the repair of oxidative DNA damage...
  66. ncbi Repair of oxidative DNA damage: mechanisms and functions
    A L Lu
    Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore 21201, USA
    Cell Biochem Biophys 35:141-70. 2001
    ..The key enzymes in the BER process are DNA glycosylases, which remove different damaged bases by cleavage of the N-glycosylic bonds between the bases and the ..
  67. ncbi Protein mimicry of DNA from crystal structures of the uracil-DNA glycosylase inhibitor protein and its complex with Escherichia coli uracil-DNA glycosylase
    C D Putnam
    Department of Molecular Biology, Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA
    J Mol Biol 287:331-46. 1999
    ....
  68. pmc Oxidative stress triggers the preferential assembly of base excision repair complexes on open chromatin regions
    Rachel Amouroux
    CEA, Institut de Radiobiologie Cellulaire et Moleculaire, 18 route du Panorama, UMR217 F 92265 Fontenay aux Roses, France
    Nucleic Acids Res 38:2878-90. 2010
    ....
  69. ncbi Interaction of checkpoint proteins Hus1/Rad1/Rad9 with DNA base excision repair enzyme MutY homolog in fission yeast, Schizosaccharomyces pombe
    Dau Yin Chang
    Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, Maryland 21201, USA
    J Biol Chem 280:408-17. 2005
    ..SpHus1 phosphorylation is substantially reduced in SpMYH Delta cells after hydrogen peroxide treatment. These data suggest that MYH may act as an adaptor to recruit checkpoint proteins to the DNA lesions...
  70. pmc Cell cycle regulation and in vitro hybrid arrest analysis of the major human uracil-DNA glycosylase
    G Slupphaug
    UNIGEN Center for Molecular Biology, University of Trondheim, Norway
    Nucleic Acids Res 19:5131-7. 1991
    ..However, specific inhibition of DNA replication with aphidicolin indicated that entrance of fibroblasts into the S-phase was not required for UDG accumulation...
  71. ncbi Expression of 8-oxoguanine DNA glycosylase 1 (OGG1) and the level of p53 and TNF-αlpha proteins in peripheral lymphocytes of patients with Alzheimer's disease
    Mateusz Dezor
    Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, Poland
    Folia Neuropathol 49:123-31. 2011
    ..It is possible that OGG1 and p53 and TNF-α proteins together or separately may be involved in pathogenesis of AD by repair of oxidative DNA damage and/or apoptosis...
  72. pmc Stoichiometry of base excision repair proteins correlates with increased somatic CAG instability in striatum over cerebellum in Huntington's disease transgenic mice
    Agathi Vassiliki Goula
    Department of Neurobiology and Genetics, Institute of Genetics and Molecular and Cellular Biology, UMR 7104 CNRS INSERM UdS, Illkirch, France
    PLoS Genet 5:e1000749. 2009
    ..We propose that the stoichiometry of BER enzymes is one critical factor underlying the tissue selectivity of somatic CAG expansion...
  73. pmc Uracil DNA glycosylase initiates degradation of HIV-1 cDNA containing misincorporated dUTP and prevents viral integration
    Amy F Weil
    Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 110:E448-57. 2013
    ..These findings establish the essential elements of this pathway and reconcile diverse observations in the literature...
  74. pmc DNA repair of oxidative DNA damage in human carcinogenesis: potential application for cancer risk assessment and prevention
    Tamar Paz-Elizur
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
    Cancer Lett 266:60-72. 2008
    ..Moreover, the combination of smoking and low OGG activity was associated with a higher risk, suggesting a potential strategy for risk assessment and prevention of lung cancer, as well as other types of cancer...
  75. pmc Dynamic relocalization of hOGG1 during the cell cycle is disrupted in cells harbouring the hOGG1-Cys326 polymorphic variant
    Luisa Luna
    Centre for Molecular Biology and Neuroscience, Institute of Medical Microbiology, University of Oslo Rikshospitalet, N 0027 Oslo, Norway
    Nucleic Acids Res 33:1813-24. 2005
    ..We investigated the cellular localization of the corresponding protein, hOGG1-Cys326, fused to EGFP and observed a dramatic effect on its localization that is explained by a change in the phosphorylation status of hOGG1...
  76. pmc Base excision repair of 8-oxoG in dinucleosomes
    Hervé Menoni
    Universite de Lyon, Laboratoire de Biologie Moleculaire de la Cellule, CNRS UMR 5239, Ecole Normale Superieure de Lyon, 46 allee d Italie, 69364 Lyon Cedex 07, France
    Nucleic Acids Res 40:692-700. 2012
    ..We show, however, that removal of histone H1 and nucleosome remodelling are both necessary and sufficient for an efficient removal of 8-oxoG in nucleosomal DNA. Finally, a model for BER of 8-oxoG in chromatin templates is suggested...
  77. ncbi The joint effect of hOGG1 single nucleotide polymorphism and smoking habit on lung cancer in Taiwan
    Chin Jung Liu
    Department of Pulmonary and Critical Care Medicine, China Medical University Hospital, Taichung, Taiwan, ROC
    Anticancer Res 30:4141-5. 2010
    ..To evaluate the association and interaction among human 8-oxoguanine DNA glycosylase 1 (hOGG1) genotypic polymorphism, smoking status and lung cancer risk in Taiwan...
  78. doi AP-site cleavage activity of tyrosyl-DNA phosphodiesterase 1
    Natalia A Lebedeva
    SB RAS Institute of Chemical Biology and Fundamental Medicine, Novosibirsk, Russia
    FEBS Lett 585:683-6. 2011
    ..Tdp1 is known to interact stably with BER proteins: DNA polymerase beta (Pol β), XRCC1, PARP1 and DNA ligase III. The data suggest a role of Tdp1 in the new APE-independent BER pathway in mammals...
  79. pmc Adenine DNA glycosylase activity of 14 human MutY homolog (MUTYH) variant proteins found in patients with colorectal polyposis and cancer
    Masanori Goto
    First Department of Pathology, Hamamatsu University School of Medicine, Japan
    Hum Mutat 31:E1861-74. 2010
    ..These results should be of great value in accurately diagnosing MAP and in fully understanding the mechanism by which MUTYH repairs DNA in which adenine is mispaired with 8-hydroxyguanine...
  80. pmc Overcoming temozolomide resistance in glioblastoma via dual inhibition of NAD+ biosynthesis and base excision repair
    Eva M Goellner
    Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, and University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, Pennsylvania 15213 1863, USA
    Cancer Res 71:2308-17. 2011
    ..Dual targeting of these two interacting pathways (DNA repair and NAD(+) biosynthesis) may prove to be an effective treatment combination for patients with resistant and recurrent GBM...
  81. pmc New functions of XPC in the protection of human skin cells from oxidative damage
    Mariarosaria D'Errico
    Department of Environment and Primary Prevention, Istituto Superiore di Sanita, Rome, Italy
    EMBO J 25:4305-15. 2006
    ..The accumulation of endogenous oxidative DNA damage might contribute to increased skin cancer risk and account for internal cancers reported for XP-C patients...
  82. ncbi Manipulation of base excision repair to sensitize ovarian cancer cells to alkylating agent temozolomide
    Melissa L Fishel
    Department of Pediatrics Section of Hematology Oncology, Herman B Wells Center for Pediatric Research, Indianapolis, Indiana 46202, USA
    Clin Cancer Res 13:260-7. 2007
    ....
  83. pmc Poly(ADP-ribose) polymerase 1 (PARP-1) binds to 8-oxoguanine-DNA glycosylase (OGG1)
    Nicole Noren Hooten
    Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA
    J Biol Chem 286:44679-90. 2011
    ..Furthermore, OGG1(-/-) cells were more sensitive to PARP inhibitors alone or in combination with a DNA-damaging agent. These findings indicate that OGG1 binding to PARP-1 plays a functional role in the repair of oxidative DNA damage...
  84. ncbi Structure and specificity of the vertebrate anti-mutator uracil-DNA glycosylase SMUG1
    Jane E A Wibley
    Cancer Research UK DNA Repair Enzyme Group, Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, United Kingdom
    Mol Cell 11:1647-59. 2003
    ..In bacteria, uracil is excised by uracil-DNA glycosylases (UDG) related to E. coli UNG, and UNG homologs are found in mammals and viruses...
  85. pmc Oxidative DNA damage correlates with cell immortalization and mir-92 expression in hepatocellular carcinoma
    Romilda Cardin
    Department of Surgery, Oncology and Gastroenterology, Section of Gastroenterology, University of Padova, Via Giustiniani 2, Padova 35128, Italy
    BMC Cancer 12:177. 2012
    ....
  86. pmc An 8-oxo-guanine repair pathway coordinated by MUTYH glycosylase and DNA polymerase lambda
    Barbara van Loon
    Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
    Proc Natl Acad Sci U S A 106:18201-6. 2009
    ..These results reveal a cellular response pathway to ROS, important to sustain genomic stability and modulate carcinogenesis...
  87. pmc Variable penetrance of metabolic phenotypes and development of high-fat diet-induced adiposity in NEIL1-deficient mice
    Harini Sampath
    Center for Research on Occupational and Environmental Toxicology, Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, USA
    Am J Physiol Endocrinol Metab 300:E724-34. 2011
    ..Collectively, these data indicate that NEIL1 deficiency results in an increased susceptibility to obesity and related complications potentially by lowering the threshold for tolerance of cellular oxidative stress in neil1(-/-) mice...
  88. doi Transition-state analysis of the DNA repair enzyme MutY
    Joe A B McCann
    Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 4M1, Canada
    J Am Chem Soc 130:5789-97. 2008
    ..Combining the experimental TS structure with the previously reported crystal structure of an abortive Michaelis complex elucidates the step-by-step catalytic sequence...
  89. doi MUTYH-associated polyposis (MAP)
    Maartje Nielsen
    Department Clinical Genetics, Leiden University Medical Centre, Albinusdreef, Leiden, The Netherlands
    Crit Rev Oncol Hematol 79:1-16. 2011
    ..Furthermore, the relationship between MUTYH and the mismatch repair genes in colorectal cancer (CRC) families is examined. Finally, the role of other base excision repair genes in polyposis and CRC patients is discussed...
  90. pmc Aag-initiated base excision repair drives alkylation-induced retinal degeneration in mice
    Lisiane B Meira
    Department of Biological Engineering and Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 106:888-93. 2009
    ..Aag heterozygotes display an intermediate level of retinal degeneration, demonstrating haploinsufficiency and underscoring that Aag expression confers a dominant retinal degeneration phenotype...
  91. pmc The metabolic syndrome resulting from a knockout of the NEIL1 DNA glycosylase
    Vladimir Vartanian
    Center for Research on Occupational and Environmental Toxicology and Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR 97239 3098, USA
    Proc Natl Acad Sci U S A 103:1864-9. 2006
    ..These data suggest an important role for NEIL1 in the prevention of the diseases associated with the metabolic syndrome...
  92. ncbi Definitive identification of mammalian 5-hydroxymethyluracil DNA N-glycosylase activity as SMUG1
    R J Boorstein
    Department of Pathology and Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York, New York 10016, USA
    J Biol Chem 276:41991-7. 2001
    ..We conclude that hSMUG1 and HMUDG are the same protein...
  93. pmc Direct repair of 3,N(4)-ethenocytosine by the human ALKBH2 dioxygenase is blocked by the AAG/MPG glycosylase
    Dragony Fu
    Department of Biological Engineering, and Biology, Center for Environmental Health Sciences, David H Koch Center for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, United States
    DNA Repair (Amst) 11:46-52. 2012
    ..These results identify human ALKBH2 as a repair enzyme for mutagenic ɛC lesions and highlight potential consequences for substrate-binding overlap between the base excision and direct reversal DNA repair pathways...
  94. pmc The Mutyh base excision repair gene influences the inflammatory response in a mouse model of ulcerative colitis
    Ida Casorelli
    Department of Environment and Primary Prevention, Istituto Superiore di Sanita, Rome, Italy
    PLoS ONE 5:e12070. 2010
    ..Since defective DNA repair genes might contribute to the increased cancer risk associated with inflammatory bowel diseases, we compared the inflammatory response of wild-type and Mutyh(-/-) mice to oxidative stress...
  95. doi Base excision repair pathway genes polymorphism in prostate and bladder cancer risk in North Indian population
    Rama Devi Mittal
    Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, Uttar Pradesh, India
    Mech Ageing Dev 133:127-32. 2012
    ..Carcinogens causes DNA damage, including oxidative lesions that are removed efficiently by the base excision repair (BER) pathway. Variations in BER genes may reduce DNA repair capacity, leading to development of urological cancers...
  96. pmc Enhanced activity of adenine-DNA glycosylase (Myh) by apurinic/apyrimidinic endonuclease (Ape1) in mammalian base excision repair of an A/GO mismatch
    H Yang
    Department of Microbiology and Molecular Genetics and the Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA and Department of Cancer Cell Biology, Harvard School of Public Health, Boston, MA 02115, USA
    Nucleic Acids Res 29:743-52. 2001
    ..Consequently, Ape1 preserves the Myh preference for A/GO over A/G and improves overall glycosylase efficiency. Our study suggests that protein-protein interactions may occur in vivo to achieve efficient BER of A/GO...
  97. doi Genetic polymorphism of DNA base-excision repair genes (APE1, OGG1 and XRCC1) and their correlation with risk of lung cancer in a Chinese population
    Zheng Li
    Department of Pathology, Third Military Medical University, Chongqing, China
    Arch Med Res 42:226-34. 2011
    ..The aim of this study was to analyze the polymorphisms of DNA BER genes (OOG1, XRCC1 and APE1) and explore their associations, and the combined effects of these variants, with risk of lung cancer...
  98. doi DNA repair capacity and acute radiotherapy adverse effects in Italian breast cancer patients
    Silvia Sterpone
    Department of Biology, University of Roma Tre, V le G Marconi 446, Rome 00146, Italy
    Mutat Res 684:43-8. 2010
    ..BC patients showed an impairment of their DNA repair capacity associated with the development of radiation sensitivity but not with polymorphisms in any of the considered genes...
  99. doi Interactive effect of cigarette smoking with human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) polymorphisms on the risk of lung cancer: a case-control study in Taiwan
    Chin Hao Chang
    Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan, Republic of China
    Am J Epidemiol 170:695-702. 2009
    ..The authors conclude that there was a noticeable modifying effect on the association between hOGG1 genotype and lung cancer risk by cigarette smoking status...
  100. pmc Redox signaling between DNA repair proteins for efficient lesion detection
    Amie K Boal
    Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
    Proc Natl Acad Sci U S A 106:15237-42. 2009
    ..These results illustrate how repair proteins might efficiently locate DNA lesions and point to a biological role for DNA-mediated CT within the cell...
  101. pmc Hopping enables a DNA repair glycosylase to search both strands and bypass a bound protein
    Mark Hedglin
    Chemical Biology Program, University of Michigan, Ann Arbor, Michigan 48109 5606, USA
    ACS Chem Biol 5:427-36. 2010
    ..This has important biological implications for the search for DNA damage because eukaryotic DNA is replete with proteins and only transiently accessible...

Research Grants64

  1. Role of Diabetes in Development of Renal Cell Carcinoma
    SAMY LEWIZ HABIB; Fiscal Year: 2013
    ....
  2. Folate Status, Genomic Uracil, and the Balance of Base Excision Repair Activity
    Michael D Wyatt; Fiscal Year: 2011
    ..Uracil in DNA is removed by uracil DNA glycosylases (UDGs) of the Base Excision Repair (BER) pathway. BER removes an array of mutagenic DNA base damage...
  3. Molecular Determinants of DNA Sliding and Hopping by a DNA Repair Glycosylase
    MENG MENG ROWLAND; Fiscal Year: 2013
    ....
  4. DNA Repair of Endogenous Lesions in Carcinogenesis
    Rabindra Roy; Fiscal Year: 2010
    ..Our preliminary results showed that DNA glycosylases (such as OGG1 and NTH1)-mediated excision activity of oxidized bases (8-oxoguanine and dihydrouracil) was ..
  5. Regulations of DNA Alkylation/Deamination Damage Repair
    Rabindra Roy; Fiscal Year: 2013
    ..The information from this study will also help to elucidate the function of other DNA glycosylases in BER pathway in combating various mutagenic and toxic DNA lesions in preventing cancer and aging...
  6. Regulatory Functions of APE1 acetylation
    KISHOR KUMAR BHAKAT; Fiscal Year: 2013
    ..pathway by repairing abasic (AP) sites generated in DNA spontaneously or after removal of damaged bases by DNA glycosylases. Besides this key role in DNA repair, APE1 acts as a transcriptional regulator that binds to several ..
  7. Mechanisms of Asbestos-Induced Alveolar Epithelial Cell Injury
    David W Kamp; Fiscal Year: 2013
    ..g. asbestos, cigarette smoke, air-borne particulate matter etc). ..
  8. Linkage of Lung Inflammation to 8-oxoguanine and OGG1
    ISTVAN STEVEN BOLDOGH; Fiscal Year: 2013
    ..Downregulation of OGG1 (but not of other oxidized-base specific DNA glycosylases) in the lungs of sensitized mice before RWPE exposure significantly decreased allergic airway inflammation...
  9. R15 AREA: Replication in the Presence of Oxidative DNA damage
    Justin Courcelle; Fiscal Year: 2012
    ..cellular assay to monitor the repair of lesion in vivo we will identify the biologically relevant oxidative DNA glycosylases that are responsible for the global repair of the genome and subseuqnetly identify the substrate lesions ..
  10. Regulation and Function of Active DNA Demethylation in Arabidopsis
    Daniel Zilberman; Fiscal Year: 2013
    ..In Aim 3, we will identify new genes required for DNA demethylation. Our studies will lead to a detailed understanding of the epigenetic reprogramming catalyzed by DNA demethylation during plant sexual reproduction. ..
  11. DNA Demethylation and Transcriptional Gene Silencing
    Jian Kang Zhu; Fiscal Year: 2013
    ..The proposed work will advance new concepts and fill major gaps in our understanding of the dynamic control of DNA methylation, and thus will contribute significantly to elucidating the molecular basis of epigenetic regulation. ..
  12. Polymorphic variants of human DNA glycosylase NEIL2 and lung cancer susceptibilit
    Tapas K Hazra; Fiscal Year: 2010
    ..The second phase is to examine blood samples from lung cancer patients to determine if there are particular variants of this protein associated with this disease and if these variants are dysfunctional. ..
  13. Metal inhibition of the base excision repair enzymes
    Anton Guliaev; Fiscal Year: 2013
    ..Understanding the mechanisms, by which toxic metals interfere with DNA repair, is relevant to developing fundamental knowledge that will aid in cancer prevention and treatment. ..
  14. Mechanisms of selective excision and oxidative repair of alkylated DNA
    Manel Camps; Fiscal Year: 2013
    ..these two specific lesions: i) oxidative demethylation by DNA dioxygenases and ii) base excision repair by DNA glycosylases. The precise determinants for the specificity and catalysis of these enzymes toward 3mA and eA remain unclear...
  15. MOLECULAR GENETICS OF HSV DNA POLYMERASE GENE
    James M Hogle; Fiscal Year: 2013
    ..The research proposed should not only provide information that could aid in drug discovery and understanding how viruses become resistant to current drugs, but aims directly to discover new anti-herpesvirus drugs. ..
  16. Coordinating Translesion DNA Synthesis Opposite Damaged DNA
    Robert L Eoff; Fiscal Year: 2010
    ..genetic code takes place the cell can respond with an arsenal of repair mechanisms including lesion specific DNA glycosylases, transferases, nucleotide/base-excision repair, and mismatch repair pathways...
  17. Mitochondrial DNA repair agents for acute lung injury
    Mark N Gillespie; Fiscal Year: 2012
    ..Herein we will test a new concept - that repair of oxidative mtDNA damage directs cell fate decisions in ALI - which, if valid, will point to an entirely new pharmacologic strategy for treating ALI and related disorders. ..
  18. DNA Repair Enzymes for the Prevention of Skin Cancer
    Amanda K McCullough; Fiscal Year: 2013
    ....
  19. Oxidative Stress, Mitochondrial Dysfunction and Aging
    JOHN NMN PAPACONSTANTINOU; Fiscal Year: 2010
    ..abstract_text> ..
  20. Mitigation of asbestos induced alveolar epithelial cell injury
    David W Kamp; Fiscal Year: 2013
    ..g. asbestos, cigarette smoke, particulate matter etc). ..
  21. Repair of Oxidized Bases in Mammalian Genomes
    Sankar Mitra; Fiscal Year: 2012
    ..are mostly repaired via the base excision repair (BER) pathway, initiated with excision of base lesions by DNA glycosylases. Accumulation of oxidized base damage without a strong phenotype in mice lacking OGG1 and NTH1, the major ..
  22. 950 MHz NMR Spectrometer with Cryogenic Probe
    DAVID JOSEPH WEBER; Fiscal Year: 2010
    ..Dr. Alex Drohat (UMB), Structure of CpG specific DNA glycosylases;7. Dr. Frank Margolis (UMB), Structure/function studies of OMP and its influence on the Na?exchanger (NCX);8...
  23. Repair of Oxidatively Damaged Guanines
    A LIEN L LU-CHANG; Fiscal Year: 2013
    ..DNA damage are repaired by base excision repair (BER), initiated with removal of base lesions by DNA glycosylases. The overall goal of this project is to study the role of selected DNA glycosylases and mismatch repair ..
  24. DNA repair deficient cells for analysis
    Robert W Sobol; Fiscal Year: 2011
    ..Gene expression knockdown of the DNA glycosylases exemplify the impact of DNA repair defects on the human transcriptome...
  25. Structure and mechanism of CpG specific DNA glycosylases
    ALEX C DROHAT; Fiscal Year: 2013
    ..Two DNA glycosylases recognize G.T lesions, thymine DNA glycosylase (TDG) and methyl binding domain IV (MBD4)...
  26. VACCINIA DNA REPLICATION
    Paula Traktman; Fiscal Year: 2013
    ..Furthermore, we will use a targeted siRNA library to identify cellular membrane-trafficking proteins that contribute to the reorganization of the ER for the purpose of replication factory assembly. ..
  27. FUNCTIONALLY TETHERED OLIGONUCLEOTIDES
    Gregory L Verdine; Fiscal Year: 2011
    ..The specific systems chosen for study are: DNA glycosylases. These enzymes initiate the repair of mutagenic base lesions residues in DNA...
  28. Structure and Function of DNA Repair Enzymes
    Susan S Wallace; Fiscal Year: 2013
    ..are to understand at the atomic level how three families of DNA repair enzymes the HhH-GPD superfamily of DNA glycosylases, the Fpg/Nei family of DNA glycosylases and the RecA-RAD51 family of recombinases, recognize and process ..
  29. EUKARYOTIC DNA ALKYLATION REPAIR
    Leona D Samson; Fiscal Year: 2013
    ....
  30. Class Switch Recombination in B Lymphocytes
    Michel C Nussenzweig; Fiscal Year: 2012
    ..It also seeks to uncover the mechanisms involved in cancer producing translocations. ..
  31. Impact of uracil DNA glycosylase on lung cancer cell sensitivity to pemetrexed
    LACHELLE DAWN WEEKS; Fiscal Year: 2013
    ....
  32. DNA-Protein Dynamics in Base Excision DNA Repair
    PATRICK O'BRIEN; Fiscal Year: 2013
    ..safeguard against these spontaneous lesions relies largely on the base excision repair (BER) pathway whereby DNA glycosylases scan the genome to locate and excise base lesions...
  33. Uracil Damage Recognition by Uracil DNA Glycosylase
    James T Stivers; Fiscal Year: 2013
    ..The characterization of the molecular interactions in this pathway provides the basis for identifying new targets for biomedical intervention in the immune response, cancer therapy and viral pathogenesis. ..
  34. Recognition and excision of nucleosomal uracils by human uracil DNA glycosylase
    Mary R Stahley; Fiscal Year: 2010
    ..The studies proposed in this application will examine this important enzyme in the biological context of the ucleosomes. ..
  35. Structural Biochemistry of DNA Dealkylation
    John A Tainer; Fiscal Year: 2012
    ..one of the most common cytotoxic and mutagenic DNA lesions, is classically repaired by lesion-specific DNA glycosylases, which excise alkylated bases to create abasic sites and initiate the base-excision repair (BER) pathway...
  36. Structure and Mechanism in DNA Excision Repair
    GREGORY LAWRENCE VERDINE; Fiscal Year: 2013
    ..The key components of BER are DNA glycosylases, professional lesion-hunting enzymes that scan the genome in search of particular kinds of base damage, then ..
  37. EXOCYCLIC DNA ADDUCTS AND OXIDATIVE DNA DAMAGE
    ARTHUR GROLLMAN; Fiscal Year: 2009
    ..We will establish three-dimensional structures and characterize the energetics of DNA glycosylases and DNA polymerases bound to their cognate DNA substrates...
  38. Repair of Radiation-Induced Crosslink Lesions of DNA
    Yinsheng Wang; Fiscal Year: 2013
    ....
  39. Mechanistic Insights into TET-Mediated Demethylation in Leukemia
    Louis C Dore; Fiscal Year: 2013
    ..Finally, we will test the role of these identified genes in hematopoietic cells and validate our findings in primary human AML samples. ..
  40. Molecular Pharmacology of Oxidative DNA Damage: Structure and Energetics
    ARTHUR PATRICK GROLLMAN; Fiscal Year: 2012
    ..We believe that "recognition" of damage by DNA glycosylases is not limited to interactions in the enzyme's active site but, rather, is part of a dynamic process ..
  41. Labeling and sequencing of 5-hmC 5-caC and 5-fC in genomic DNA - Resubmission 0
    Chuan He; Fiscal Year: 2013
    ....
  42. Graduate Training at the Chemistry Biology Interface
    Katherine L Seley-Radtke; Fiscal Year: 2013
    ..S100B Bound to Small Molecules that Inhibit p53 Binding", "The Importance of APE1 in the Stimulation of DNA Glycosylases", "Characterization of the Relationship between TDG and APE1", and "Chemically characterizing the active ..
  43. MITDNA MUTAGENESIS BY ENVIRONMENTAL CARCINOGENS
    Keshav Singh; Fiscal Year: 2003
    ..The proposed study will fill a major gap in our understanding of the mechanisms of mitDNA mutagenesis induced by environmental carcinogens which has direct relevance in on the induction of mitochondrial diseases. ..
  44. Dynamics of Normal and Damaged DNA Under Relaxed and Supercoiled Conditions
    Hashim M Al-Hashimi; Fiscal Year: 2013
    ....
  45. DME-INTERACTING PROTEIN 1 REGULATES DEMETHYLATOIN AND REPRODUCTION IN ARABIDOPSIS
    Wenyan Xiao; Fiscal Year: 2009
    ..In Arabidopsis, DEMETER (DME) belongs to a family of DNA glycosylases that excise damaged or mispaired bases in the base excision DNA repair...
  46. Xanthine DNA Glycosylase in Mammalian Systems
    Weiguo Cao; Fiscal Year: 2010
    ..Defects in DNA repair pathways are associated with genome instability and carcinogenesis. Study of repair caused by DNA deamination is essential for understanding the potential link between DNA repair and human diseases such as cancer. ..
  47. DNA repair and lg class switching
    Janet Stavnezer; Fiscal Year: 2007
    ..In Aim 4 we will explore how the mutations are introduced into Ig S regions by determining if the translesion DNA polymerase iota is involved in the error-prone repair of S regions and if this involvement is regulated by cytokines. ..
  48. Repair of oxidative damage in mammalian genomes
    Tapas K Hazra; Fiscal Year: 2010
    ..in all organisms occurs primarily via the DNA base excision repair (BER) pathway, initiated with excision by DNA glycosylases. Only two previously characterized mammalian DNA glycosylases, OGG1 and NTH1, are thought to excise most of ..
  49. BIOPHYSICAL AND SCANNING FORCE MICROSCOPY STUDIES
    DOROTHY ERIE; Fiscal Year: 2001
    ..Both types of damage result in abasic sites in the DNA (the deaminated bases are removed by specific DNA glycosylases) and both are repaired by BER...
  50. ENDONUCLEASE V EXPRESSION IN HUMAN CELLS
    Earl Henderson; Fiscal Year: 1992
    ....
  51. COMBATING ALKYLATING AGENT RESISTANCE IN HUMAN GLIOMAS
    JOHN SILBER; Fiscal Year: 2002
    ..In an effort to define the role of 3-MAG in clinical drug resistance, enzyme levels will be correlated with response to alkylator adjuvant therapy and clinical course. ..
  52. GENETIC SUSCEPTIBILITY TO VINYL CHLORIDE INDUCED CANCER
    Roland Valdes; Fiscal Year: 2000
    ..The results will provide a genetic-based model useful in approaching a variety of other diseases caused from environmental exposure to xenobiotics. ..
  53. REACTION COORDINATE ANALYSES--URACIL DNA GLYCOSYLASES
    NICOLE HORENSTEIN; Fiscal Year: 2003
    ..Abstract): This proposal presents a research plan for a comparative mechanistic analysis of uracil DNA glycosylases (UDG's) from E. coli and Vaccina virus, and mismatch-specific uracil DNA glycosylase (MUG) from E. coli...
  54. FUNCTION FOR VPR AND VPX OF PRIMATE LENTIVIRUSES
    Mario Stevenson; Fiscal Year: 2009
    ..It is expected that these studies will more fully define the contribution of nuclear import activities of Vpr and i Vpx proteins to virus replication in vitro and in vivo. ..
  55. HUMAN DNA REPAIR ENZYMES FOR REDOX AND ALKYLATION DAMAGE
    BRUCE F DEMPLE; Fiscal Year: 2010
    ..In BER, DNA glycosylases remove altered bases to generate abasic sites, which are further processed in several steps dependent on the ..
  56. FORMATION, MUTAGENICITY & REPAIR OF PHOTOHYDRATES IN DNA
    George Teebor; Fiscal Year: 1999
    ....
  57. MECHANISMS OF DRUG RESISTANCE IN PEDIATRIC BRAIN TUMORS
    MICHAEL BOBOLA; Fiscal Year: 2000
    ..The cell line and tissue data will add to our understanding of tumor resistance to alkylating-agent-based chemotherapy and aid in designing more effective chemotherapy protocols. ..
  58. Structure and Function of Clustered DNA Lesions
    Carlos de Los Santos; Fiscal Year: 2007
    ..DNA incision studies using purified DNA glycosylases or nuclear cell extracts showed that some MDS can be cleaved readily generating toxic DSB, while others are ..
  59. REGULATION OF DNA REPAIR IN HUMAN CARCINOGENSIS
    MICHAEL SIROVER; Fiscal Year: 1993
    ..The objectives of this proposal are: 1) To examine the immunology and sequence homology of human uracil DNA glycosylases. Enzymes structure will be examined by peptide mapping and identification of the glycosylase monoclonal ..
  60. METABOLISM OF DNA
    Huber Warner; Fiscal Year: 1980
    ..Thus, thymine-dimer initiated repair and uracil initiated repair may share a common repair pathway in vivo. ..
  61. Linking Enzyme and DNA Dynamics: The Mechanism of Extrahelical Damaged based dete
    Jared Parker; Fiscal Year: 2009
    ..The goal of this work is to elucidate how these machines locate these sites, with the long term goal of using the recognition principles to design molecules that efficiently direct these enzymes to specific damaged sites in the genome. ..
  62. MECHANISM BASED INHIBITION OF DNA GLYCOSYLASES
    Gregory Verdine; Fiscal Year: 1999
    ..The present study will focus on a prominent class of repair proteins, DNA glycosylases, which catalyze the hydrolytic excision of damaged bases from DNA...
  63. DNA repair deficient human cells for genomic variation analysis
    JAY GEORGE; Fiscal Year: 2009
    ..of producing stable human cell lines with complete deficiency in DNA repair proteins, specifically DNA glycosylases. Further, we propose to characterize each newly developed cell line with respect to mRNA and protein ..
  64. SUBSTRATE RECOGNITION MECHANISM OF DNA REPAIR ENZYMES
    Michael Wyatt; Fiscal Year: 2001
    ..Base excision repair initiated by DNA glycosylases helps to maintain genomic stability by removing damaged bases from the genome...