Spiroiminodihydantoin lesions derived from guanine oxidation: structures, energetics, and functional implications.

Reactive oxygen species present in the cell generate DNA damage. One of the major oxidation products of guanine in DNA, 8-oxo-7,8-dihydroguanine, formed by loss of two electrons, is among the most extensively studied base lesions. The further removal of two electrons from this product can yield spiroiminodihydantoin (Sp) R and S stereoisomers. Both in vitro and in vivo experiments have shown that the Sp stereoisomers are highly mutagenic, causing G --> T and G --> C transversions. Hence, they are of interest as examples of endogenous DNA damage that may initiate cancer. To interpret the mutagenic properties of the Sp lesions, an understanding of their structural properties is needed. To elucidate these structural effects, we have carried out computational investigations at the level of the Sp-modified base and nucleoside. At the base level, quantum mechanical geometry optimization studies have revealed exact mirror image symmetry of the R and S stereoisomers, with a near-perpendicular geometry of the two rings. At the nucleoside level, an extensive survey of the potential energy surface by molecular mechanics calculations using AMBER has provided three-dimensional potential energy maps. These maps reveal that the range and flexibility of the glycosidic torsion angles are significantly more restricted in both stereoisomeric adducts than in unmodified 2'-deoxyguanosine. The structural and energetic results suggest that the unusual geometric, steric, and hydrogen bonding properties of these lesions underlie their mutagenicity. In addition, stereoisomer-specific differences indicate the possibility that their processing by cellular replication and repair enzymes may be differentially affected by their absolute configuration.

[1]  G. Michael Blackburn,et al.  Nucleic acids in chemistry and biology , 2007 .

[2]  Kent D. Sugden,et al.  Recognition of the oxidized lesions spiroiminodihydantoin and guanidinohydantoin in DNA by the mammalian base excision repair glycosylases NEIL1 and NEIL2. , 2005, DNA repair.

[3]  William L. Neeley,et al.  Urea lesion formation in DNA as a consequence of 7,8-dihydro-8-oxoguanine oxidation and hydrolysis provides a potent source of point mutations. , 2005, Chemical research in toxicology.

[4]  William L. Neeley,et al.  In Vivo Bypass Efficiencies and Mutational Signatures of the Guanine Oxidation Products 2-Aminoimidazolone and 5-Guanidino-4-nitroimidazole* , 2004, Journal of Biological Chemistry.

[5]  M. Evans,et al.  Oxidative DNA damage and disease: induction, repair and significance. , 2004, Mutation research.

[6]  N. Geacintov,et al.  Oxidative DNA Damage Associated with Combination of Guanine and Superoxide Radicals and Repair Mechanisms via Radical Trapping* , 2004, Journal of Biological Chemistry.

[7]  C. Burrows,et al.  Spermine participates in oxidative damage of guanosine and 8-oxoguanosine leading to deoxyribosylurea formation. , 2004, Journal of the American Chemical Society.

[8]  D. Fisher.  The p53 tumor suppressor: Critical regulator of life & death in cancer , 2001, Apoptosis.

[9]  N. Geacintov,et al.  DNA lesions derived from the site selective oxidation of Guanine by carbonate radical anions. , 2003, Chemical research in toxicology.

[10]  M. Leipold,et al.  Recognition and removal of oxidized guanines in duplex DNA by the base excision repair enzymes hOGG1, yOGG1, and yOGG2. , 2003, Biochemistry.

[11]  William L. Neeley,et al.  The hydantoin lesions formed from oxidation of 7,8-dihydro-8-oxoguanine are potent sources of replication errors in vivo. , 2003, Biochemistry.

[12]  Zukang Feng,et al.  The Nucleic Acid Database. , 2002, Acta crystallographica. Section D, Biological crystallography.

[13]  C. Burrows,et al.  In vitro nucleotide misinsertion opposite the oxidized guanosine lesions spiroiminodihydantoin and guanidinohydantoin and DNA synthesis past the lesions using Escherichia coli DNA polymerase I (Klenow fragment). , 2002, Biochemistry.

[14]  Santanu K. Mishra,et al.  An ab initio theoretical study of electronic structure and properties of 2′‐deoxyguanosine in gas phase and aqueous media , 2002, J. Comput. Chem..

[15]  J. Cadet,et al.  [18O]-Labeled Singlet Oxygen as a Tool for Mechanistic Studies of 8-Oxo-7,8-Dihydroguanine Oxidative Damage: Detection of Spiroiminodihydantoin, Imidazolone and Oxazolone Derivatives , 2002, Biological chemistry.

[16]  Toshinori Suzuki,et al.  Nicotine‐modulated formation of spiroiminodihydantoin nucleoside via 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine in 2′‐deoxyguanosine–hypochlorous acid reaction , 2002, FEBS letters.

[17]  U. Pischel,et al.  A comparative photomechanistic study (spin trapping, EPR spectroscopy, transient kinetics, photoproducts) of nucleoside oxidation (dG and 8-oxodG) by triplet-excited acetophenones and by the radicals generated from alpha-oxy-substituted derivatives through Norrish-type I cleavage. , 2002, Journal of the American Chemical Society.

[18]  J. Hoeijmakers,et al.  Premature Aging in Mice Deficient in DNA Repair and Transcription , 2002, Science.

[19]  Alison L. Livingston,et al.  Inherited variants of MYH associated with somatic G:C→T:A mutations in colorectal tumors , 2002, Nature Genetics.

[20]  U. Pischel,et al.  Spiroiminodihydantoin is a major product in the photooxidation of 2'-deoxyguanosine by the triplet states and oxyl radicals generated from hydroxyacetophenone photolysis and dioxetane thermolysis. , 2002, Organic letters.

[21]  S. Tannenbaum,et al.  Oxidation of 7,8-dihydro-8-oxoguanine affords lesions that are potent sources of replication errors in vivo. , 2002, Biochemistry.

[22]  S. Tannenbaum,et al.  A novel nitroimidazole compound formed during the reaction of peroxynitrite with 2',3',5'-tri-O-acetyl-guanosine. , 2001, Journal of the American Chemical Society.

[23]  S. Finkelstein,et al.  Frequent Allelic Imbalance and Loss of Protein Expression of the DNA Repair Gene hOGG1 in Head and Neck Squamous Cell Carcinoma , 2001, Laboratory Investigation.

[24]  Y. Gu,et al.  Alteration of DNA base excision repair enzymes hMYH and hOGG1 in hydrogen peroxide resistant transformed human breast cells. , 2001, Medical science monitor : international medical journal of experimental and clinical research.

[25]  T. Lindahl,et al.  Age-related and tissue-specific accumulation of oxidative DNA base damage in 7,8-dihydro-8-oxoguanine-DNA glycosylase (Ogg1) deficient mice. , 2001, Carcinogenesis.

[26]  Zhongmao Guo,et al.  Does oxidative damage to DNA increase with age? , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[27]  C. Burrows,et al.  The pH-dependent role of superoxide in riboflavin-catalyzed photooxidation of 8-oxo-7,8-dihydroguanosine. , 2001, Organic letters.

[28]  H. Ohshima,et al.  Formation of spiroiminodihydantoin nucleoside by reaction of 8-oxo-7,8-dihydro-2'-deoxyguanosine with hypochlorous acid or a myeloperoxidase-H(2)O(2)-Cl(-) system. , 2001, Chemical research in toxicology.

[29]  C. Burrows,et al.  Characterization of hydantoin products from one-electron oxidation of 8-oxo-7,8-dihydroguanosine in a nucleoside model. , 2001, Chemical research in toxicology.

[30]  S. Toyokuni,et al.  Spontaneous loss-of-function mutations of the 8-oxoguanine DNA glycosylase gene in mice and exploration of the possible implication of the gene in senescence. , 2001, Free radical biology & medicine.

[31]  S R Tannenbaum,et al.  Spiroiminodihydantoin is the major product of the 8-oxo-7,8-dihydroguanosine reaction with peroxynitrite in the presence of thiols and guanosine photooxidation by methylene blue. , 2001, Organic letters.

[32]  H. You,et al.  Genetic changes of hOGG1 and the activity of oh8Gua glycosylase in colon cancer. , 2001, European journal of cancer.

[33]  Kent D. Sugden,et al.  Direct oxidation of guanine and 7,8-dihydro-8-oxoguanine in DNA by a high-valent chromium complex: a possible mechanism for chromate genotoxicity. , 2001, Chemical research in toxicology.

[34]  M. Leipold,et al.  Removal of hydantoin products of 8-oxoguanine oxidation by the Escherichia coli DNA repair enzyme, FPG. , 2000, Biochemistry.

[35]  Junmei Wang,et al.  How well does a restrained electrostatic potential (RESP) model perform in calculating conformational energies of organic and biological molecules? , 2000, J. Comput. Chem..

[36]  G. Gyapay,et al.  Alterations of the DNA repair gene OGG1 in human clear cell carcinomas of the kidney. , 2000, Cancer research.

[37]  Nicolas Leulliot,et al.  Ground-State Properties of Nucleic Acid Constituents Studied by Density Functional Calculations. 3. Role of Sugar Puckering and Base Orientation on the Energetics and Geometry of 2‘-Deoxyribonucleosides and Ribonucleosides , 2000 .

[38]  C. Burrows,et al.  Characterization of spiroiminodihydantoin as a product of one-electron oxidation of 8-Oxo-7,8-dihydroguanosine. , 2000, Organic letters.

[39]  N. Tretyakova,et al.  Peroxynitrite-induced reactions of synthetic oligonucleotides containing 8-oxoguanine. , 1999, Chemical research in toxicology.

[40]  S. Broyde,et al.  Stereochemical origin of opposite orientations in DNA adducts derived from enantiomeric anti-benzo[a]pyrene diol epoxides with different tumorigenic potentials. , 1999, Biochemistry.

[41]  N. Malats,et al.  Human cancer, carcinogenic exposures and mutation spectra. , 1999, Mutation research.

[42]  J. Radicella,et al.  Base excision repair of 8-hydroxyguanine protects DNA from endogenous oxidative stress. , 1999, Biochimie.

[43]  C. Burrows,et al.  Insertion of dGMP and dAMP during in vitro DNA synthesis opposite an oxidized form of 7,8-dihydro-8-oxoguanine. , 1999, Nucleic acids research.

[44]  H. Kamiya,et al.  The mutations induced by oxidatively damaged nucleotides, 5-formyl-dUTP and 5-hydroxy-dCTP,in Escherichia coli. , 1998, Nucleic acids research.

[45]  B. Dutrillaux,et al.  Mutations in OGG1, a gene involved in the repair of oxidative DNA damage, are found in human lung and kidney tumours , 1998, Oncogene.

[46]  Sheila S. David,et al.  Chemistry of Glycosylases and Endonucleases Involved in Base-Excision Repair. , 1998, Chemical reviews.

[47]  S. Linn,et al.  Formation, Prevention, and Repair of DNA Damage by Iron/Hydrogen Peroxide* , 1997, The Journal of Biological Chemistry.

[48]  G. Verdine,et al.  A mammalian DNA repair enzyme that excises oxidatively damaged guanines maps to a locus frequently lost in lung cancer , 1997, Current Biology.

[49]  H M Berman,et al.  Crystal studies of B-DNA: the answers and the questions. , 1997, Biopolymers.

[50]  J. Cadet,et al.  Oxidative damage to DNA: formation, measurement, and biological significance. , 1997, Reviews of physiology, biochemistry and pharmacology.

[51]  T. Halgren.  Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94 , 1996, J. Comput. Chem..

[52]  H. Berman,et al.  Geometric Parameters in Nucleic Acids: Sugar and Phosphate Constituents , 1996 .

[53]  B. Epe,et al.  DNA damage profiles induced by oxidizing agents. , 1996, Reviews of physiology, biochemistry and pharmacology.

[54]  P. Kollman,et al.  A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids, and Organic Molecules , 1995 .

[55]  B Demple,et al.  Repair of oxidative damage to DNA: enzymology and biology. , 1994, Annual review of biochemistry.

[56]  P. Kollman,et al.  A well-behaved electrostatic potential-based method using charge restraints for deriving atomic char , 1993 .

[57]  T. Lindahl.  Instability and decay of the primary structure of DNA , 1993, Nature.

[58]  J. Miller,et al.  A repair system for 8-oxo-7,8-dihydrodeoxyguanine. , 1992, Biochemistry.

[59]  J. Miller,et al.  Evidence that MutY and MutM combine to prevent mutations by an oxidatively damaged form of guanine in DNA. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

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

[61]  T. Hayden,et al.  Prediction of DNA structure from sequence: A build‐up technique , 1989, Biopolymers.

[62]  A. Becke,et al.  Density-functional exchange-energy approximation with correct asymptotic behavior. , 1988, Physical review. A, General physics.

[63]  Parr,et al.  Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. , 1988, Physical review. B, Condensed matter.

[64]  R. H. Ritchie,et al.  Dielectric effects in biopolymers: The theory of ionic saturation revisited , 1985 .

[65]  Wolfram Saenger,et al.  Principles of Nucleic Acid Structure , 1983 .

[66]  W. Olson.  Computational studies of polynucleotide flexibility. , 1982, Nucleic acids research.

[67]  W. Olson,et al.  How flexible is the furanose ring? 1. A comparison of experimental and theoretical studies , 1982 .

[68]  W. Olson.  Three-state models of furanose pseudorotation. , 1981, Nucleic acids research.

[69]  R. Goyal,et al.  Electrochemical and enzymic oxidation of biological purines , 1981 .

[70]  W. Olson.  Spatial configuration of ordered polynucleotide chains. V. Conformational energy estimates of helical structure , 1978 .

[71]  W. Olson,et al.  Spatial configuration of ordered polynucleotide chains. 3. Polycyclonucleotides. , 1976, Journal of the American Chemical Society.

[72]  José Elguero,et al.  The Tautomerism of heterocycles , 1976 .

[73]  W. Olson.  Syn–Anti effects on the spatial configuration of polynucleotide chains , 1973, Biopolymers.

[74]  M. Sundaralingam,et al.  Conformational analysis of the sugar ring in nucleosides and nucleotides. A new description using the concept of pseudorotation. , 1972, Journal of the American Chemical Society.

[75]  H. M. Sobell,et al.  The crystal structure of a hydrogen bonded complex of deoxyguanosine and 5-bromodeoxycytidine. , 1965, Acta crystallographica.

[76]  H. M. Sobell,et al.  THE CRYSTAL STRUCTURE OF A HYDROGEN BONDED COMPLEX OF ADENOSINE AND 5-BROMOURIDINE. , 1965, Acta crystallographica.