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2005 | 52 | 1 | 167-178
Article title

Inhibition of DNA repair glycosylases by base analogs and tryptophan pyrolysate, Trp-P-1.

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Abstracts
EN
DNA base analogs, 2,4,5,6-substituted pyrimidines and 2,6-substituted purines were tested as potential inhibitors of E. coli Fpg protein (formamidopyrimidine -DNA glycosylase). Three of the seventeen compounds tested revealed inhibitory properties. 2-Thioxanthine was the most efficient, inhibiting 50% of 2,6-diamino-4-hydroxy-5N-methyl-formamidopyrimidine (Fapy-7MeG) excision activity at 17.1 μM concentration. The measured Kgi was 4.44 ± 0.15 μM. Inhibition was observed only when the Fpg protein was first challenged to its substrate followed by the addition of the base analog, suggesting uncompetitive (catalytic) inhibition. For two other compounds, 2-thio- or 2-oxo-4,5,6-substituted pyrimidines, IC50 was only 343.3 ± 58.6 and 350 ± 24.4 μM, respectively. No change of the Fpg glycosylase activity was detected in the presence of Fapy-7MeG, up to 5 μM. We also investigated the effect of DNA structure modified by tryptophan pyrolysate (Trp-P-1) on the activity of base excision repair enzymes: Escherichia coli and human DNA glycosylases of oxidized (Fpg, Nth) and alkylated bases (TagA, AlkA, and ANPG), and for bacterial AP endonuclease (Xth protein). Trp-P-1, which changes the secondary DNA structure into non-B, non-Z most efficiently inhibited excision of alkylated bases by the AlkA glycosylase (IC50 = 1 μM). The ANPG, TagA, and Fpg proteins were also inhibited although to a lesser extent (IC50 = 76.5 μM, 96 μM, and 187.5 μM, respectively). Trp-P-1 also inhibited incision of DNA at abasic sites by the β-lyase activity of the Fpg and Nth proteins, and to a lesser extent by the Xth AP endonuclease. Thus, DNA conformation is critical for excision of damaged bases and incision of abasic sites by DNA repair enzymes.
Publisher

Year
Volume
52
Issue
1
Pages
167-178
Physical description
Dates
published
2005
received
2005-01-17
accepted
2005-02-28
Contributors
  • Department of Molecular Biology, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warszawa, Poland
  • Department of Molecular Biology, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warszawa, Poland
  • Department of Molecular Biology, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warszawa, Poland
author
  • Groupe "Reparation de l'ADN," CNRS Unite Mixte de Recherche 8126, Institut Gustave Roussy, Villejuif Cedex, France
  • Laboratory of Experimental Pharmacology, Medical Research Center, Polish Academy of Sciences, Warszawa, Poland
author
  • Department of Molecular Biology, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warszawa, Poland
References
  • Amara P, Serre L, Castaing B, Thomas A. (2004) Insights into the DNA repair process by the formamidopyrimidine-DNA glycosylase investigated by molecular dynamics. Protein Sci.; 13: 2009-21.
  • Bailly V, Verly WG, O'Connor T, Laval J. (1989) Mechanism of DNA strand nicking at apurinic/apyrimidinic sites by Escherichia coli [formamidopyrimidine]DNA glycosylase. Biochem J.; 262: 581-9.
  • Beaman AG. (1954) New syntheses of purine. J Am Chem Soc.; 76: 5633-6.
  • Bendich A, Tinker JF, Brown GB. (1948) A synthesis of isoguanine labeled with isotopic nitrogen. J Am Chem Soc.; 70: 3109-13.
  • Boiteux S, Belleney J, Roques BP, Laval J. (1984) Two rotameric forms of open ring 7 methylguanine are present in alkylated polynucleotides. Nucleic Acids Res.; 12: 5429-39.
  • Boiteux S, Costa de Oliveira R, Laval J. (1985) The Escherichia coli O6-methylguanine-DNA methyltransferase does not repair promutagenic O6-methylguanine residues when present in Z-DNA. J Biol Chem.; 260: 8711-5.
  • Boiteux S, O'Connor TR, Laval J. (1987) Formamidopyrimidine-DNA glycosylase of Escherichia coli: cloning and sequencing of the fpg structural gene and overproduction of the protein. EMBO J.; 6: 3177-83.
  • Boiteux S, O'Connor TR, Lederer F, Gouyette A, Laval J. (1990) Homogeneous Escherichia coli FPG protein. A DNA glycosylase which excises imidazole ring-opened purines and nicks DNA at apurinic/apyrimidinic sites. J Biol Chem.; 265: 3916-22.
  • Boiteux S, Gajewski E, Laval J. Dizdaroglu M. (1992) Substrate specificity of the Escherichia coli Fpg protein (formamidopyrimidine-DNA glycosylase): excision of purine lesions in DNA produced by ionizing radiation or photosensitization. Biochemistry.; 31: 106-10.
  • Bradford MM. (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilising the principle of protein-dye binding. Anal Biochem.; 72: 248-55.
  • Cussac C, Laval F. (1996) Reduction of the toxicity and mutagenicity of aziridine in mammalian cells harboring the Escherichia coli fpg gene. Nucleic Acids Res.; 24: 1742-6.
  • Das A, Rajagopalan L, Mathura VS, Rigby SJ, Mitra S, Hazra TK. (2004) Identification of a zinc finger domain in the human NEIL2 (Nei-like-2) protein. J Biol Chem.; 279: 47132-8.
  • Dizdaroglu M, Laval J, Boiteux S. (1993) Substrate specificity of the Escherichia coli endonuclease III: excision of thymine- and cytosine-derived lesions in DNA produced by radiation-generated free radicals. Biochemistry.; 32: 12105-11.
  • Dizdaroglu M, Bauche C, Rodriguez H, Laval J. (2000) Novel substrates of Escherichia coli Nth protein and its kinetics for excision of modified bases from DNA damaged by free radicals. Biochemistry.; 39: 5586-92.
  • Dolan ME, Pegg AE. (1997) O6-benzylguanine and its role in chemotherapy. Clin Cancer Res.; 3: 837-47.
  • Drohat AC, Kwon K, Krosky DJ, Stivers JT. (2002) 3-Methyladenine DNA glycosylase I is an unexpected helix-hairpin-helix superfamily member. Nat Struct Biol.; 9: 659-64.
  • Duarte V, Gasparutto D, Jaquinod M, Cadet J. (2000) In vitro DNA synthesis opposite oxazolone and repair of this DNA damage using modified oligonucleotides. Nucleic Acids Res.; 28: 1555-63.
  • Graves RJ, Felzenszwalb I, Laval J, O'Connor TR. (1992) Excision of 5'-terminal deoxyribose phosphate from damaged DNA is catalyzed by the Fpg protein of Escherichia coli. J Biol Chem.; 267: 14429-35.
  • Gros L, Saparbaev MK, Laval J. (2002) Enzymology of the repair of free radicals-induced DNA damage. Oncogene.; 21: 8905-25.
  • Hayashi M, Hisanaga Y, Yamauchi K, Kinoshita M. (1980) Methylation of thiouracils and thioxanthines with trimethyl phosphate. Syn Comm.; 10: 791-8.
  • Hazra TK, Izumi T, Boldogh I, Imhoff B, Kow YW, Jaruga P, Dizdaroglu M, Mitra S. (2002a) Identification and characterization of a human DNA glycosylase for repair of modified bases in oxidatively damaged DNA. Proc Natl Acad Sci USA.; 99: 3523-8.
  • Hazra TK, Kow YW, Hatahet Z, Imhoff B, Boldogh I, Mokkapati SK, Mitra S, Izumi T. (2002b) Identification and characterization of a novel human DNA glycosylase for repair of cytosine-derived lesions. J Biol Chem.; 277: 30417-20.
  • Huebsch W, Pfleiderer W. (1988) 150. Pteridines. Synthesis and properties of 8-substituted 2-thiolumazines. Helv Chim Acta.; 71: 1379-91.
  • Inohara T, Tarui M, Mihara Y, Doi M, Ishida T. (1995) Binding specificity of mutagenic tryptophan pyrolysates for DNA conformation: spectroscopic and viscometric studies. Chem Pharm Bull.; 43: 1607-13.
  • Jurado J, Saparbaev M, Matray TJ, Greenberg MM, Laval J. (1998) The ring fragmentation product of thymidine C5-hydrate when present in DNA is repaired by the Escherichia coli Fpg and Nth proteins. Biochemistry.; 37: 7757-63.
  • Kamiński ZW, Domino EF. (1987) Computer program for calculation of kinetic and pharmacologic parameters using a 'direct linear plot' derived algorithm. Comput Methods Programs Biomed.; 24: 41-5.
  • Kazimierczuk Z, Shugar D. (1974) Preparation of some N-methyl isoguanines via 6-methylthio-2-oxopurines, and of 8-methylisoguanine. Acta Biochim Polon.; 21: 455-63.
  • Kazimierczuk Z, Lipski M, Shugar D. (1972) Intermediates in the synthesis of purines and pteridines. Selective hydrolysis of chloropyrimidines. Acta Biochim Polon.; 19: 359-66.
  • Kuo CF, McRee DE, Cunningham RP, Tainer JA. (1992a) Crystallization and crystallographic characterization of the iron-sulfur-containing DNA-repair enzyme endonuclease III from Escherichia coli. J Mol Biol.; 227: 347-51.
  • Kuo CF, McRee DE, Fisher CL, O'Handley SF, Cunningham RP, Tainer JA. (1992b) Atomic structure of the DNA repair [4Fe-4S] enzyme endonuclease III. Science.; 258: 434-40.
  • Kuo CF, McRee DE, Cunningham RP, Tainer JA. (1993) Purification, crystallization and space group determination of DNA repair enzyme exonuclease III from E. coli. J Mol Biol.; 229: 239-42.
  • Lagravère C, Malfoy B, Leng M, Laval J. (1984) Ring-opened alkylated guanine is not repaired in Z-DNA. Nature.; 310: 798-800.
  • Larson ED, Drummond JT. (2001) Human mismatch repair and G*T mismatch binding by hMutSalpha in vitro is inhibited by adriamycine, actinomycine D, and nogalamycin. J Biol Chem.; 276: 9775-83.
  • Laval J. (1977) Two enzymes are required from strand incision in repair of alkylated DNA. Nature.; 269: 829-32
  • Laval J, Pierre J, Laval F. (1981) Release of 7-methylguanine residues from alkylated DNA by extracts of Micrococcus luteus and Escherichia coli. Proc Natl Acad Sci USA.; 78: 852-5.
  • Leblanc JP, Martin B, Cadet J, Laval J. (1982) Uracil-DNA glycosylase. Purification and properties of uracil-DNA glycosylase from Micrococcus luteus. J Biol Chem.; 257: 3477-83.
  • Lichtenberg D, Bergmann F, Neiman Z. (1972) Tautomerism and ionization processes in 6-thioxanthine and its N-methyl derivatives. J Chem Soc.; 1676-81.
  • Mori T, Shimoi K, Sasaki YF, Wakabayashi K, Nagao M, Kinae N. (1993) 3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) inhibits the removal of both cyclobutane dimers and (6-4) photoproducts from the DNA of ultraviolet-irradiated E. coli. Carcinogenesis.; 14: 1475-8.
  • O'Connor TR, Laval F. (1990). Isolation and structure of a cDNA expressing mammalian 3-methyladenine-DNA glycosylase. EMBO J.; 9: 3337-42.
  • O'Connor TR, Laval J. (1991) Human cDNA expressing a functional DNA glycosylase excising 3-methyladenine and 7-methylguanine. Biochem Biophys Res Commun.; 176: 1170-77.
  • Ohgaki H, Hasegawa H, Kato T, Suenaga M, Ubukata M, Sato S, Takayama S, Sugimura T. (1986) Carcinogenicity in mice and rats of heterocyclic amines in cooked foods. Environ Health Perspect.; 67: 129-34.
  • Papesch V, Schroeder EF. (1951) Synthesis of 1-mono- and 1,3-disubstituted 6-aminouracils. diuretic activity. J Org Chem.; 16: 1879-90.
  • Pfleiderer W, Fink H. (1962) Umsetzungen mit 4-Chlorcytosin. Liebigs Ann Chem.; 657: 149-55.
  • Price JA, Heller E, Goldthwait DA. (1983) The release of 3-methyladenine from nucleosomal DNA by a 3-methyladenine DNA glycosylase. Carcinogenesis.; 4: 145-52.
  • Sambrook J, Fritsch EF, Maniatis T. (1989) Molecular Cloning, 2nd edn. Cold Spring Harbor Lab. Press. New York.
  • Saparbaev M, Laval J. (1994) Excision of hypoxanthine from DNA containing dIMP residues by the Escherichia coli, yeast, rat, and human alkylpurine DNA glycosylases. Proc Natl Acad Sci USA.; 91: 5873-7.
  • Saparbaev M, Kleibl K, Laval J. (1995) Escherichia coli, Saccharomyces cerevisiae, rat and human 3-methyladenine DNA glycosylases repair 1,N6-ethenoadenine when present in DNA. Nucleic Acids Res.; 23: 3750-5.
  • Sasaki YF, Yamada H, Shimoi K, Kinae N, Tomita I, Matsumura H, Ohta T, Shirasu Y. (1992) Enhancing effects of heterocyclic amines and beta-carbolines on the induction of chromosome aberrations in cultured mammalian cells. Mutat Res.; 269: 79-95.
  • Schold SC Jr, Kokkinakis DM, Chang SM, Berger MS, Hess KR, Schiff D, Robins HI, Mehta MP, Fink KL, Davis RL, Prados MD. (2004) O6-benzylguanine suppression of O6-alkylguanine-DNA alkyltransferase in anaplastic gliomas. Neuro-oncol.; 6: 28-32.
  • Shimoi K, Kawabata H, Tomita I. (1992) Enhancing effect of heterocyclic amines and beta-carbolines on UV or chemically induced mutagenesis in E. coli. Mutat Res.; 268: 287-95.
  • Shimoi K, Miyamura R, Mori T, Todo T, Ohtsuka E, Wakabayashi K. (1996) 3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) inhibits the binding activity of T4 endonuclease V to UV-damaged DNA. Carcinogenesis.; 17: 1279-83.
  • Speina E, Cieśla JM, Wójcik J, Bajek M, Kuśmierek JT, Tudek B. (2001) The pyrimidine ring-opened derivative of 1,N6-ethenoadenine is excised from DNA by the Escherichia coli Fpg and Nth proteins. J Biol Chem.; 276: 21821-7.
  • Taylor EC, Chain CK. (1952) Pteridines VII. The Synthesis of 2-Alkylaminopteridines. J Am Chem Soc.; 1644-7.
  • Tchou J, Kasai H, Shibutani S, Chung MH, Laval J, Grollman AP, Nishimura S. (1991) 8-Oxoguanine (8-hydroxyguanine) DNA glycosylase and its substrate specificity. Proc Natl Acad Sci USA.; 88: 4690-4.
  • Tchou J, Bodepudi V, Shibutani S, Antoshechkin I, Miller J, Grollman AP, Johnson F. (1994) Substrate specificity of Fpg protein. Recognition and cleavage of oxidatively damaged DNA. J Biol Chem.; 269: 15318-24.
  • Thomas L, Yang CH, Goldthwait DA. (1982) Two DNA glycosylases in Escherichia coli which release primarily 3-methyladenine. Biochemistry.; 21: 1162-9.
  • Traube W. (1904) Der Aufbau der Xanthinbasen aus der Cyanessigsaure. Synthese des Hypoxanthins and Adenins. Liebigs Ann Chem.; 331: 64-88.
  • Tudek B, Laval J, Boiteux S. (1993) SOS-independent mutagenesis in lacZ induced by methylene blue plus visible light. Mol Gen Genet.; 236: 433-9.
  • Tudek B, Van Zeeland AA, Kuśmierek JT, Laval J. (1998) Activity of Escherichia coli DNA-glycosylases on DNA damaged by methylating and ethylating agents and influence of 3-substituted adenine derivatives. Mutat Res.; 407: 169-76.
  • Watanabe M, Ohta T. (1993) Analysis of mutational specificity induced by heterocyclic amines in the lacZ gene of Escherichia coli. Carcinogenesis.; 14: 1149-53.
  • Yamazaki A, Kumashiro I, Takenishi T, Ikehara M. (1968) Synthesis of thio-AICA, 6-thioxanthine, isoguanosine analogs and their ribosides. Chem Pharm Bull.; 16: 2172-81.
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bwmeta1.element.bwnjournal-article-abpv52i1p167kz
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