dna formamidopyrimidine glycosylase


Summary: A DNA repair enzyme that is an N-glycosyl hydrolase with specificity for DNA-containing ring-opened N(7)-methylguanine residues.

Top Publications

  1. Zharkov D, Grollman A. MutY DNA glycosylase: base release and intermediate complex formation. Biochemistry. 1998;37:12384-94 pubmed
    ..The MutY-DNA intermediate complex is highly stable and hinders access by Fpg to DNA, thereby avoiding a double-strand break. Cross-linking of MutY to DNA may play an important role in the regulation of base excision repair. ..
  2. Jain R, Kumar P, Varshney U. A distinct role of formamidopyrimidine DNA glycosylase (MutM) in down-regulation of accumulation of G, C mutations and protection against oxidative stress in mycobacteria. DNA Repair (Amst). 2007;6:1774-85 pubmed publisher
    ..smegmatis as opposed to an A in E. coli. Our studies highlight the importance and the distinctive features of Fpg mediated DNA repair in mycobacteria...
  3. Bandaru V, Sunkara S, Wallace S, Bond J. A novel human DNA glycosylase that removes oxidative DNA damage and is homologous to Escherichia coli endonuclease VIII. DNA Repair (Amst). 2002;1:517-29 pubmed
    ..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. ..
  4. Boiteux S, O Connor T, Laval J. Formamidopyrimidine-DNA glycosylase of Escherichia coli: cloning and sequencing of the fpg structural gene and overproduction of the protein. EMBO J. 1987;6:3177-83 pubmed
    ..The nucleotide sequence of the fpg gene is composed of 809 base pairs and codes for a protein of 269 amino acids with a calculated mol. wt of 30.2 kd. ..
  5. Zharkov D, Rosenquist T, Gerchman S, Grollman A. Substrate specificity and reaction mechanism of murine 8-oxoguanine-DNA glycosylase. J Biol Chem. 2000;275:28607-17 pubmed
    ..A substituent at C6 and a keto group at C8 are required for cleavage. The proposed mechanism of 8-oxoG excision involves protonation of O(8) or the deoxyribose oxygen moiety. ..
  6. Fromme J, Verdine G. DNA lesion recognition by the bacterial repair enzyme MutM. J Biol Chem. 2003;278:51543-8 pubmed
    ..Furthermore, the structure of MutM in complex with DNA containing an alternative substrate, dihydrouracil, demonstrates how MutM is able to recognize lesions other than oxoG. ..
  7. Van Der Kemp P, Thomas D, Barbey R, de Oliveira R, Boiteux S. 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. Proc Natl Acad Sci U S A. 1996;93:5197-202 pubmed
    ..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. ..
  8. Zharkov D, Ishchenko A, Douglas K, Nevinsky G. Recognition of damaged DNA by Escherichia coli Fpg protein: insights from structural and kinetic data. Mutat Res. 2003;531:141-56 pubmed
    ..Biochemistry 41 (2002) 7540]. Stopped-flow kinetic analysis that has allowed the dissection of Fpg catalysis in time [Fedorova et al., Biochemistry 41 (2002) 1520] is also correlated with the structural data. ..
  9. Matsumoto Y, Zhang Q, Takao M, Yasui A, Yonei S. Escherichia coli Nth and human hNTH1 DNA glycosylases are involved in removal of 8-oxoguanine from 8-oxoguanine/guanine mispairs in DNA. Nucleic Acids Res. 2001;29:1975-81 pubmed
    ..Furthermore, we found that human hNTH1 protein, a homolog of E.coli Nth protein, has similar DNA glycosylase/AP lyase activity that removes 8-oxoG from 8-oxoG/G mispairs. ..

More Information


  1. Blaisdell J, Hatahet Z, Wallace S. A novel role for Escherichia coli endonuclease VIII in prevention of spontaneous G-->T transversions. J Bacteriol. 1999;181:6396-402 pubmed
    ..This was confirmed by showing that, indeed, endo VIII can recognize 8-oxoG in vitro. ..
  2. D Ham C, Romieu A, Jaquinod M, Gasparutto D, Cadet J. Excision of 5,6-dihydroxy-5,6-dihydrothymine, 5,6-dihydrothymine, and 5-hydroxycytosine from defined sequence oligonucleotides by Escherichia coli endonuclease III and Fpg proteins: kinetic and mechanistic aspects. Biochemistry. 1999;38:3335-44 pubmed
  3. Michaels M, Pham L, Cruz C, Miller J. MutM, a protein that prevents G.C----T.A transversions, is formamidopyrimidine-DNA glycosylase. Nucleic Acids Res. 1991;19:3629-32 pubmed
    ..C----T.A transversions. This in vivo characterization correlates well with the mutagenic potential of one of the lesions Fapy-DNA glycosylase removes, 8-oxo-7,8-dihydro-2'-deoxyguanine (8-OxodG). ..
  4. Muhlenhoff U. The FAPY-DNA glycosylase (Fpg) is required for survival of the cyanobacterium Synechococcus elongatus under high light irradiance. FEMS Microbiol Lett. 2000;187:127-32 pubmed
  5. Czeczot H, Tudek B, Lambert B, Laval J, Boiteux S. Escherichia coli Fpg protein and UvrABC endonuclease repair DNA damage induced by methylene blue plus visible light in vivo and in vitro. J Bacteriol. 1991;173:3419-24 pubmed
    ..Therefore, one of the physiological functions of Fpg protein might be to repair DNA base damage induced by photosensitizers and light. ..
  6. Serre L, Pereira de J sus K, Boiteux S, Zelwer C, Castaing B. Crystal structure of the Lactococcus lactis formamidopyrimidine-DNA glycosylase bound to an abasic site analogue-containing DNA. EMBO J. 2002;21:2854-65 pubmed publisher
    ..In addition, the modelling of the 8-oxoguanine residue allows us to define an enzyme pocket that may accommodate the extrahelical oxidized base...
  7. Coste F, Ober M, Carell T, Boiteux S, Zelwer C, Castaing B. Structural basis for the recognition of the FapydG lesion (2,6-diamino-4-hydroxy-5-formamidopyrimidine) by formamidopyrimidine-DNA glycosylase. J Biol Chem. 2004;279:44074-83 pubmed publisher
    ..The significant differences between the Fpg recognition modes of 8-oxodG and FapydG provide new insights into the Fpg substrate specificity...
  8. Vidal A, Hickson I, Boiteux S, Radicella J. Mechanism of stimulation of the DNA glycosylase activity of hOGG1 by the major human AP endonuclease: bypass of the AP lyase activity step. Nucleic Acids Res. 2001;29:1285-92 pubmed
    ..These data indicate that, in the presence of HAP1, the BER of 8-oxoG residues can be highly efficient by bypassing the AP lyase activity of hOGG1 and thus excluding a potentially rate limiting step. ..
  9. David Cordonnier M, Laval J, O NEILL P. Clustered DNA damage, influence on damage excision by XRS5 nuclear extracts and Escherichia coli Nth and Fpg proteins. J Biol Chem. 2000;275:11865-73 pubmed
    ..Therefore, this large inhibition of the excision of DHT by the presence of an opposite AP site may minimize the formation of double-strand breaks in the processing of DNA clustered damages. ..
  10. Hill J, Hazra T, Izumi T, Mitra S. Stimulation of human 8-oxoguanine-DNA glycosylase by AP-endonuclease: potential coordination of the initial steps in base excision repair. Nucleic Acids Res. 2001;29:430-8 pubmed
    ..These results suggest coordinated functions of OGG1 and APE1, and possibly other enzymes, in the DNA base excision repair pathway. ..
  11. Hori M, Yonei S, Sugiyama H, Kino K, Yamamoto K, Zhang Q. Identification of high excision capacity for 5-hydroxymethyluracil mispaired with guanine in DNA of Escherichia coli MutM, Nei and Nth DNA glycosylases. Nucleic Acids Res. 2003;31:1191-6 pubmed
    ..In E.coli, the 5hmU-DNA glycosylase activities of MutM, Nei and Nth may play critical roles in the repair of 5hmU:G mispairs to avoid 5mC to T transitions. ..
  12. Collins A, Dusinska M, Horvathova E, Munro E, Savio M, Stetina R. Inter-individual differences in repair of DNA base oxidation, measured in vitro with the comet assay. Mutagenesis. 2001;16:297-301 pubmed
    ..This new DNA repair assay is simple, rapid and requires only small quantities of lymphocyte extract (obtainable from 10 ml blood). ..
  13. Rosenquist T, Zharkov D, Grollman A. Cloning and characterization of a mammalian 8-oxoguanine DNA glycosylase. Proc Natl Acad Sci U S A. 1997;94:7429-34 pubmed
    ..Isolation of the mouse ogg1 gene makes it possible to modulate its expression in mice and to explore the involvement of oxidative DNA damage and associated repair processes in aging and cancer. ..
  14. Tchou J, Kasai H, Shibutani S, Chung M, Laval J, Grollman A, et al. 8-oxoguanine (8-hydroxyguanine) DNA glycosylase and its substrate specificity. Proc Natl Acad Sci U S A. 1991;88:4690-4 pubmed
  15. Dany A, Tissier A. A functional OGG1 homologue from Arabidopsis thaliana. Mol Genet Genomics. 2001;265:293-301 pubmed
    ..Thus, we have demonstrated that AtOGG1 is not only a structural but also a functional eukaryotic OGG1 homologue. ..
  16. Fromme J, Verdine G. Structural insights into lesion recognition and repair by the bacterial 8-oxoguanine DNA glycosylase MutM. Nat Struct Biol. 2002;9:544-52 pubmed
    ..These structures reveal that the MutM active site performs the multiple steps of base-excision and 3' and 5' nicking with minimal rearrangement of the DNA backbone. ..
  17. Audebert M, Radicella J, Dizdaroglu M. Effect of single mutations in the OGG1 gene found in human tumors on the substrate specificity of the Ogg1 protein. Nucleic Acids Res. 2000;28:2672-8 pubmed
    ..Taken together the results show that the mutant forms alpha-hOgg1-Gln(46) and alpha-hOgg1-His(154) found in human tumors are defective in their catalytic capacities. ..
  18. Gulston M, Fulford J, Jenner T, de Lara C, O Neill P. Clustered DNA damage induced by gamma radiation in human fibroblasts (HF19), hamster (V79-4) cells and plasmid DNA is revealed as Fpg and Nth sensitive sites. Nucleic Acids Res. 2002;30:3464-72 pubmed
    ..4-2.0- and 1.8-fold, respectively. Therefore, clustered DNA damage is induced in cells by sparsely ionizing radiation and their yield is significantly greater than that of prompt DSB. ..
  19. Sidorkina O, Laval J. Role of the N-terminal proline residue in the catalytic activities of the Escherichia coli Fpg protein. J Biol Chem. 2000;275:9924-9 pubmed
  20. Bruner S, Norman D, Verdine G. Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA. Nature. 2000;403:859-66 pubmed
    ..One known mutation, R154H, converts hOGG1 to a promutator by relaxing the specificity of the enzyme for the base opposite oxoG. ..
  21. Bjoras M, Luna L, Johnsen B, Hoff E, Haug T, Rognes T, et al. Opposite base-dependent reactions of a human base excision repair enzyme on DNA containing 7,8-dihydro-8-oxoguanine and abasic sites. EMBO J. 1997;16:6314-22 pubmed
  22. Davidsen T, Amundsen E, Rødland E, Tønjum T. DNA repair profiles of disease-associated isolates of Neisseria meningitidis. FEMS Immunol Med Microbiol. 2007;49:243-51 pubmed
    ..These results provide a basis for further studies aimed at resolving the genotype/phenotype relationships of meningococcal genome variability and mutator activity. ..
  23. Gilboa R, Zharkov D, Golan G, Fernandes A, Gerchman S, Matz E, et al. Structure of formamidopyrimidine-DNA glycosylase covalently complexed to DNA. J Biol Chem. 2002;277:19811-6 pubmed
    ..A deep hydrophobic pocket in the active site is positioned to accommodate an everted base. Structural analysis of the Fpg-DNA complex reveals essential features of damage recognition and the catalytic mechanism of Fpg. ..
  24. Dogliotti E, Fortini P, Pascucci B, Parlanti E. The mechanism of switching among multiple BER pathways. Prog Nucleic Acid Res Mol Biol. 2001;68:3-27 pubmed
    ..These findings raise the interesting possibility that different BER pathways might be acting as a function of the cell cycle stage. ..
  25. Saparbaev M, Sidorkina O, Jurado J, Privezentzev C, Greenberg M, Laval J. Repair of oxidized purines and damaged pyrimidines by E. coli Fpg protein: different roles of proline 2 and lysine 57 residues. Environ Mol Mutagen. 2002;39:10-7 pubmed
    ..coli Fpg). Based on the biochemical assays, together with the crystal structure of T. thermophilus HB8 Fpg protein, we propose a two-nucleophile model for the enzymatic catalysis. ..
  26. Wiederholt C, Delaney M, Greenberg M. Interaction of DNA containing Fapy.dA or its C-nucleoside analogues with base excision repair enzymes. Implications for mutagenesis and enzyme inhibition. Biochemistry. 2002;41:15838-44 pubmed
    ..dA) opposite dC (K(D) = 7.1 +/- 1.5 nM). A duplex containing a beta-C-Fapy.dA:T base pair is an effective inhibitor (K(I) = 3.5 +/- 0.3 nM) of repair of Fapy.dA by Fpg, suggesting the C-nucleoside may have useful therapeutic properties. ..
  27. Castaing B, Boiteux S, Zelwer C. DNA containing a chemically reduced apurinic site is a high affinity ligand for the E. coli formamidopyrimidine-DNA glycosylase. Nucleic Acids Res. 1992;20:389-94 pubmed
    ..In contrast, no such retardation band was obtained between the FPG protein and double-stranded DNA containing an intact apurinic site or single-stranded DNA containing either an intact or a reduced apurinic site. ..
  28. Sidorenko V, Rot M, Filipenko M, Nevinsky G, Zharkov D. Novel DNA glycosylases from Mycobacterium tuberculosis. Biochemistry (Mosc). 2008;73:442-50 pubmed
    ..Fpg and Nei homologs from M. tuberculosis can play an important role in protection of bacteria against genotoxic stress caused by oxidative burst in macrophages. ..
  29. Tudek B. Imidazole ring-opened DNA purines and their biological significance. J Biochem Mol Biol. 2003;36:12-9 pubmed
    ..Bacterial enzymes include E.coli formamidopyrimidine-DNA-glycosylase (Fpg protein), endonuclease III (Nth protein) and endonuclease VIII (Nei protein). ..
  30. Boiteux S, O Connor T, Lederer F, Gouyette A, Laval J. Homogeneous Escherichia coli FPG protein. A DNA glycosylase which excises imidazole ring-opened purines and nicks DNA at apurinic/apyrimidinic sites. J Biol Chem. 1990;265:3916-22 pubmed
    ..coli. The contribution of the AP-nicking activity associated with the FPG protein represents 10-20% of the total EDTA-resistant AP-nicking activities in E. coli. ..
  31. Fedorova O, Nevinsky G, Koval V, Ishchenko A, Vasilenko N, Douglas K. Stopped-flow kinetic studies of the interaction between Escherichia coli Fpg protein and DNA substrates. Biochemistry. 2002;41:1520-8 pubmed
    ..The results obtained provide direct evidence of conformational transitions of the Fpg protein during the catalytic process. The significance of these results for the functioning of Fpg protein is discussed. ..
  32. Bjørås M, Seeberg E, Luna L, Pearl L, Barrett T. Reciprocal "flipping" underlies substrate recognition and catalytic activation by the human 8-oxo-guanine DNA glycosylase. J Mol Biol. 2002;317:171-7 pubmed
    ..It has been possible to identify a mechanism whereby the catalytic residue Lys 249 is "primed" for nucleophilic attack of the N-glycosidic bond. ..
  33. Hatahet Z, Kow Y, Purmal A, Cunningham R, Wallace S. New substrates for old enzymes. 5-Hydroxy-2'-deoxycytidine and 5-hydroxy-2'-deoxyuridine are substrates for Escherichia coli endonuclease III and formamidopyrimidine DNA N-glycosylase, while 5-hydroxy-2'-deoxyuridine is a substrate for uracil DNA N-g. J Biol Chem. 1994;269:18814-20 pubmed
    ..Analysis of crude extracts obtained from wild type and endonuclease III deletion mutants of E. coli correlated well with data obtained with the purified enzymes. ..
  34. Kohno T, Shinmura K, Tosaka M, Tani M, Kim S, Sugimura H, et al. Genetic polymorphisms and alternative splicing of the hOGG1 gene, that is involved in the repair of 8-hydroxyguanine in damaged DNA. Oncogene. 1998;16:3219-25 pubmed
    ..These results suggest that the oh8Gua levels are maintained at a steady level, even though multiple hOGG1 proteins are produced due to genetic polymorphisms, mutations and alternative splicing of the hOGG1 gene. ..
  35. Boiteux S, Gajewski E, Laval J, Dizdaroglu M. Substrate specificity of the Escherichia coli Fpg protein (formamidopyrimidine-DNA glycosylase): excision of purine lesions in DNA produced by ionizing radiation or photosensitization. Biochemistry. 1992;31:106-10 pubmed
    ..The Fpg protein also excised FapyGua and 8-OH-Gua from visible light/MB-treated DNA. The presence of these products in the supernatant fractions confirmed their excision.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  36. Lavrukhin O, Lloyd R. Involvement of phylogenetically conserved acidic amino acid residues in catalysis by an oxidative DNA damage enzyme formamidopyrimidine glycosylase. Biochemistry. 2000;39:15266-71 pubmed
    ..Sodium borohydride trapping of wild-type Fpg and its E3Q and E174Q mutants on 8-oxoguanosine or AP site containing DNA correlated with the relative activity of the mutants on either of these substrates. ..
  37. Hazra T, Izumi T, Boldogh I, Imhoff B, Kow Y, Jaruga P, et al. Identification and characterization of a human DNA glycosylase for repair of modified bases in oxidatively damaged DNA. Proc Natl Acad Sci U S A. 2002;99:3523-8 pubmed
    ..The tissue-specific levels of NEH1 and OGG1 mRNAs are distinct, and S phase-specific increase in NEH1 at both RNA and protein levels suggests that NEH1 is involved in replication-associated repair of oxidized bases. ..
  38. David Cordonnier M, Laval J, O NEILL P. Recognition and kinetics for excision of a base lesion within clustered DNA damage by the Escherichia coli proteins Fpg and Nth. Biochemistry. 2001;40:5738-46 pubmed
  39. Fromme J, Bruner S, Yang W, Karplus M, Verdine G. Product-assisted catalysis in base-excision DNA repair. Nat Struct Biol. 2003;10:204-11 pubmed
    ..To our knowledge, the present example represents the first documented case of product-assisted catalysis in an enzyme-catalyzed reaction. ..
  40. Morland I, Rolseth V, Luna L, Rognes T, Bjørås M, Seeberg E. Human DNA glycosylases of the bacterial Fpg/MutM superfamily: an alternative pathway for the repair of 8-oxoguanine and other oxidation products in DNA. Nucleic Acids Res. 2002;30:4926-36 pubmed
    ..It thus appears that hFPG1 has properties similar to mammalian OGG1 in preventing mutations arising from misincorporation of A across 8-oxoG and could function as a back-up repair activity for OGG1 in ogg1(-/-) mice. ..
  41. Saitoh T, Shinmura K, Yamaguchi S, Tani M, Seki S, Murakami H, et al. Enhancement of OGG1 protein AP lyase activity by increase of APEX protein. Mutat Res. 2001;486:31-40 pubmed
  42. Boiteux S, Radicella J. The human OGG1 gene: structure, functions, and its implication in the process of carcinogenesis. Arch Biochem Biophys. 2000;377:1-8 pubmed
    ..A review of the recent literature on the mammalian Ogg1 proteins, the main repair system involved in the elimination of this mutagenic lesion, is presented. ..
  43. Pearson C, Shikazono N, Thacker J, O Neill P. Enhanced mutagenic potential of 8-oxo-7,8-dihydroguanine when present within a clustered DNA damage site. Nucleic Acids Res. 2004;32:263-70 pubmed
    ..The data suggest that at clustered damage sites, depending on lesion spacing, the action of Fpg is compromised and post-replication processing of lesions by MutY is the most important mechanism for protection against mutagenesis. ..
  44. Swartley J, Stephens D. Co-transcription of a homologue of the formamidopyrimidine-DNA glycosylase (fpg) and lysophosphatidic acid acyltransferase (nlaA) in Neisseria meningitidis. FEMS Microbiol Lett. 1995;134:171-6 pubmed
    ..We further show that the meningococcal fpg is co-transcribed with nlaA, encoding a lysophosphatidic acid acyltransferase, and suggest that the DNA repair enzyme may be involved in the regulation of nlaA or its gene product...
  45. Castaing B, Fourrey J, Hervouet N, Thomas M, Boiteux S, Zelwer C. AP site structural determinants for Fpg specific recognition. Nucleic Acids Res. 1999;27:608-15 pubmed
    ..This comparative study provides new information about the molecular mechanism involved in the Fpg AP lyase activity. ..
  46. Zaika E, Perlow R, Matz E, Broyde S, Gilboa R, Grollman A, et al. Substrate discrimination by formamidopyrimidine-DNA glycosylase: a mutational analysis. J Biol Chem. 2004;279:4849-61 pubmed
    ..His-89 and Lys-217 help determine the specificity of Fpg in recognizing the oxidatively damaged base, while Arg-108 provides specificity for bases positioned opposite the lesion. ..
  47. Zharkov D, Shoham G, Grollman A. Structural characterization of the Fpg family of DNA glycosylases. DNA Repair (Amst). 2003;2:839-62 pubmed
  48. Koval V, Kuznetsov N, Zharkov D, Ishchenko A, Douglas K, Nevinsky G, et al. Pre-steady-state kinetics shows differences in processing of various DNA lesions by Escherichia coli formamidopyrimidine-DNA glycosylase. Nucleic Acids Res. 2004;32:926-35 pubmed
    ..The data obtained provide evidence that several fast sequential conformational changes occur in Fpg after binding to its substrate, converting the protein into a catalytically active conformation. ..
  49. Perlow Poehnelt R, Zharkov D, Grollman A, Broyde S. Substrate discrimination by formamidopyrimidine-DNA glycosylase: distinguishing interactions within the active site. Biochemistry. 2004;43:16092-105 pubmed
  50. Dherin C, Radicella J, Dizdaroglu M, Boiteux S. Excision of oxidatively damaged DNA bases by the human alpha-hOgg1 protein and the polymorphic alpha-hOgg1(Ser326Cys) protein which is frequently found in human populations. Nucleic Acids Res. 1999;27:4001-7 pubmed
    ..Furthermore, both proteins efficiently complement the mutator phenotype of the fpg mutY mutant of Escherichia coli. ..
  51. Sugahara M, Mikawa T, Kumasaka T, Yamamoto M, Kato R, Fukuyama K, et al. Crystal structure of a repair enzyme of oxidatively damaged DNA, MutM (Fpg), from an extreme thermophile, Thermus thermophilus HB8. EMBO J. 2000;19:3857-69 pubmed publisher
  52. Hazra T, Hill J, Izumi T, Mitra S. Multiple DNA glycosylases for repair of 8-oxoguanine and their potential in vivo functions. Prog Nucleic Acid Res Mol Biol. 2001;68:193-205 pubmed
    ..The physiological significance of multiple OGGs and their in vivo reaction mechanisms remain to be elucidated by further studies. ..
  53. De Boeck M, Lardau S, Buchet J, Kirsch Volders M, Lison D. Absence of significant genotoxicity in lymphocytes and urine from workers exposed to moderate levels of cobalt-containing dust: a cross-sectional study. Environ Mol Mutagen. 2000;36:151-60 pubmed