Substrate specificity of the Escherichia coli Fpg protein (formamidopyrimidine-DNA glycosylase): excision of purine lesions in DNA produced by ionizing radiation or photosensitization.

We have investigated the excision of a variety of modified bases from DNA by the Escherichia coli Fpg protein (formamidopyrimidine-DNA glycosylase) [Boiteux, S., O'Connor, T. R., Lederer, F., Gouyette, A., & Laval, J. (1990) J. Biol. Chem. 265, 3916-3922]. DNA used as a substrate was modified either by exposure to ionizing radiation or by photosensitization using visible light in the presence of methylene blue (MB). The technique of gas chromatography/mass spectrometry, which can unambiguously identify and quantitate pyrimidine- and purine-derived lesions in DNA, was used for analysis of hydrolyzed and derivatized DNA samples. Thirteen products resulting from pyrimidines and purines were detected in gamma-irradiated DNA, whereas only the formation of 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua) and 8-hydroxyguanine (8-OH-Gua) was observed in visible light/MB-treated DNA. Analysis of gamma-irradiated DNA after incubation with the Fpg protein followed by precipitation revealed that the Fpg protein significantly excised 4,6-diamino-5-formamidopyrimidine (FapyAde), FapyGua, and 8-OH-Gua. The excision of a small but detectable amount of 8-hydroxyadenine was also observed. The detection of these products in the supernatant fractions of the same samples confirmed their excision by the enzyme. Nine pyrimidine-derived lesions were not excised. 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)

[1]  L. Breimer.  Molecular mechanisms of oxygen radical carcinogenesis and mutagenesis: The role of dna base damage , 2006, Molecular carcinogenesis.

[2]  W. Schulz,et al.  Formation of 8-hydroxy(deoxy)guanosine and generation of strand breaks at guanine residues in DNA by singlet oxygen. , 1991, Biochemistry.

[3]  S. Boiteux,et al.  Escherichia coli Fpg protein and UvrABC endonuclease repair DNA damage induced by methylene blue plus visible light in vivo and in vitro , 1991, Journal of bacteriology.

[4]  M. Chung,et al.  8-oxoguanine (8-hydroxyguanine) DNA glycosylase and its substrate specificity. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[5]  T. O'Connor,et al.  Physiological properties and repair of apurinic/apyrimidinic sites and imidazole ring-opened guanines in DNA. , 1990, Mutation research.

[6]  R. Cunningham,et al.  Enzymatic recognition of DNA modifications induced by singlet oxygen and photosensitizers. , 1990, Nucleic acids research.

[7]  F. Lederer,et al.  Homogeneous Escherichia coli FPG protein. A DNA glycosylase which excises imidazole ring-opened purines and nicks DNA at apurinic/apyrimidinic sites. , 1990, The Journal of biological chemistry.

[8]  B. Van Houten,et al.  UvrABC nuclease complex repairs thymine glycol, an oxidative DNA base damage. , 1990, Mutation research.

[9]  M. Dizdaroglu,et al.  Hydrogen peroxide-induced base damage in deoxyribonucleic acid. , 1990, Radiation research.

[10]  R. Floyd,et al.  Methylene blue plus light mediates 8-hydroxy 2'-deoxyguanosine formation in DNA preferentially over strand breakage. , 1990, Nucleic acids research.

[11]  A. Sancar,et al.  A new mechanism for repairing oxidative damage to DNA: (A)BC excinuclease removes AP sites and thymine glycols from DNA. , 1989, Biochemistry.

[12]  M. Bichara,et al.  Excision of the imidazole ring-opened form of N-2-aminofluorene-C(8)-guanine adduct in poly(dG-dC) by Escherichia coli formamidopyrimidine-DNA glycosylase. , 1989, Carcinogenesis.

[13]  T. O'Connor,et al.  Mechanism of DNA strand nicking at apurinic/apyrimidinic sites by Escherichia coli [formamidopyrimidine]DNA glycosylase. , 1989, The Biochemical journal.

[14]  R. Floyd,et al.  Methylene blue plus light mediates 8-hydroxyguanine formation in DNA. , 1989, Archives of biochemistry and biophysics.

[15]  O. Aruoma,et al.  Iron ion-dependent modification of bases in DNA by the superoxide radical-generating system hypoxanthine/xanthine oxidase. , 1989, The Journal of biological chemistry.

[16]  T. O'Connor,et al.  Physical association of the 2,6-diamino-4-hydroxy-5N-formamidopyrimidine-DNA glycosylase of Escherichia coli and an activity nicking DNA at apurinic/apyrimidinic sites. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[17]  R. Cunningham,et al.  Purification and characterization of Escherichia coli endonuclease III from the cloned nth gene. , 1989, Biochemistry.

[18]  Steen Steenken,et al.  Purine bases, nucleosides, and nucleotides: aqueous solution redox chemistry and transformation reactions of their radical cations and e- and OH adducts , 1989 .

[19]  Sagripanti Jl,et al.  Site-specific oxidative DNA damage at polyguanosines produced by copper plus hydrogen peroxide. , 1989 .

[20]  T. O'Connor,et al.  Formamidopyrimidine‐DNA glycosylase of Escherichia coli: cloning and sequencing of the fpg structural gene and overproduction of the protein. , 1987, The EMBO journal.

[21]  H. Sies,et al.  Biochemistry of oxidative stress , 1986 .

[22]  M. Dizdaroglu,et al.  Characterization of free radical-induced base damage in DNA at biologically relevant levels. , 1986, Analytical biochemistry.

[23]  S. Weitzman,et al.  Phagocytes as carcinogens: malignant transformation produced by human neutrophils. , 1985, Science.

[24]  M. Dizdaroglu,et al.  Application of capillary gas chromatography-mass spectrometry to chemical characterization of radiation-induced base damage of DNA: implications for assessing DNA repair processes. , 1985, Analytical biochemistry.

[25]  P. Cerutti.  Prooxidant states and tumor promotion. , 1985, Science.

[26]  L. Breimer.  Enzymatic excision from γ-irradiated polydeoxyribonucleotids of adenine residues whose imidazole rings have been rypture , 1984 .

[27]  Serge Boiteux,et al.  Two rotameric forms of open ring 7-methylguanine are present in alkylated polynucleotides , 1984, Nucleic Acids Res..

[28]  T. Lindahl,et al.  DNA glycosylase activities for thymine residues damaged by ring saturation, fragmentation, or ring contraction are functions of endonuclease III in Escherichia coli. , 1984, The Journal of biological chemistry.

[29]  B. Halliwell,et al.  DNA damage by superoxide-generating systems in relation to the mechanism of action of the anti-tumour antibiotic adriamycin. , 1983, Biochimica et biophysica acta.

[30]  B. Ames,et al.  Dietary carcinogens and anticarcinogens. Oxygen radicals and degenerative diseases. , 1983, Science.

[31]  L. Breimer.  Urea--DNA glycosylase in mammalian cells. , 1983, Biochemistry.

[32]  G. Margison,et al.  Enzymatic release of 7-methylguanine from methylated DNA by rodent liver extracts. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[33]  R. Lorentzen,et al.  Role of superoxide in deoxyribonucleic acid strand scission. , 1980, Biochemistry.

[34]  T. Lindahl,et al.  Release of 7-methylguanine residues whose imidazole rings have been opened from damaged DNA by a DNA glycosylase from Escherichia coli. , 1979, Nucleic acids research.

[35]  M. Dizdaroglu.  Chemical determination of free radical-induced damage to DNA. , 1991, Free radical biology & medicine.

[36]  M. Dizdaroglu.  Gas chromatography-mass spectrometry of free radical-induced products of pyrimidines and purines in DNA. , 1990, Methods in enzymology.

[37]  E. Gajewski,et al.  Quantitative measurement of radiation-induced base products in DNA using gas chromatography-mass spectrometry. , 1989, Radiation research.

[38]  B. Epe,et al.  DNA damage by oxygen radicals and excited state species: a comparative study using enzymatic probes in vitro. , 1988, Chemico-biological interactions.

[39]  S. Wallace.  AP endonucleases and DNA glycosylases that recognize oxidative DNA damage. , 1988, Environmental and molecular mutagenesis.

[40]  A. Sancar,et al.  DNA repair enzymes. , 1988, Annual review of biochemistry.

[41]  M. Symons.  Application of electron spin resonance spectroscopy to the study of the effects of ionising radiation on DNA and DNA complexes , 1987 .