Mutagenicity of oxidized DNA precursors in living cells: Roles of nucleotide pool sanitization and DNA repair enzymes, and translesion synthesis DNA polymerases.

The base moieties of DNA precursors in the nucleotide pool are subjected to oxidative damage, and the formation of damaged DNA precursors is an important source of mutagenesis. 8-Hydroxy-2'-deoxyguanosine 5'-triphosphate, also known by the name of its keto-enol tautomer as 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate, and 2-hydroxy-2'-deoxyadenosine 5'-triphosphate have been identified as the major products of in vitro oxidation reactions. The mutagenicities of these damaged precursors in living cells will be summarized in this review. In addition, the roles of the nucleotide pool sanitization and DNA repair enzymes, and the translesion synthesis DNA polymerases will be described.

[1]  Y. Nakabeppu Molecular genetics and structural biology of human MutT homolog, MTH1. , 2001, Mutation research.

[2]  M. Yamada,et al.  Involvement of Y-Family DNA Polymerases in Mutagenesis Caused by Oxidized Nucleotides in Escherichia coli , 2006, Journal of bacteriology.

[3]  H. Kamiya,et al.  2-Hydroxy-dATP is incorporated opposite G by Escherichia coli DNA polymerase III resulting in high mutagenicity. , 2000, Nucleic acids research.

[4]  Yoshihiro Yamamoto,et al.  Suppression of spontaneous and hydrogen peroxide‐induced mutations by a MutT‐type nucleotide pool sanitization enzyme, the Escherichia coli Orf135 protein , 2003, Genes to cells : devoted to molecular & cellular mechanisms.

[5]  H. Kamiya Mutations Induced by Oxidized DNA Precursors and Their Prevention by Nucleotide Pool Sanitization Enzymes , 2007 .

[6]  A. Yasui,et al.  Escherichia coli Nth and human hNTH1 DNA glycosylases are involved in removal of 8-oxoguanine from 8-oxoguanine/guanine mispairs in DNA. , 2001, Nucleic acids research.

[7]  H. Harashima,et al.  Effects of base excision repair proteins on mutagenesis by 8-oxo-7,8-dihydroguanine (8-hydroxyguanine) paired with cytosine and adenine. , 2010, DNA repair.

[8]  M. Yamada,et al.  Mutagenesis induced by oxidized DNA precursors: roles of Y family DNA polymerases in Escherichia coli. , 2005, Chemical research in toxicology.

[9]  H. Maki,et al.  MutT protein specifically hydrolyses a potent mutagenic substrate for DNA synthesis , 1992, Nature.

[10]  B. Ames,et al.  Dietary carcinogens and anti-carcinogens. , 1984, Journal of toxicology. Clinical toxicology.

[11]  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.

[12]  S. Kuramitsu,et al.  UvrA and UvrB enhance mutations induced by oxidized deoxyribonucleotides. , 2007, DNA repair.

[13]  H. Harashima,et al.  Correlation between the Phosphohydrolase Activity of the Escherichia coli Orf135 (NudG) Protein and Mutation Suppression , 2007 .

[14]  H. Kamiya Mutagenic potentials of damaged nucleic acids produced by reactive oxygen/nitrogen species: approaches using synthetic oligonucleotides and nucleotides: survey and summary. , 2003, Nucleic acids research.

[15]  H. Harashima,et al.  Suppression of mutagenesis by 8-hydroxy-2'-deoxyguanosine 5'-triphosphate (7,8-dihydro-8-oxo-2'-deoxyguanosine 5'-triphosphate) by human MTH1, MTH2, and NUDT5. , 2010, Free radical biology & medicine.

[16]  A. McLennan,et al.  The Nudix hydrolase superfamily , 2005, Cellular and Molecular Life Sciences CMLS.

[17]  L. Gold,et al.  Endogenous mutagens and the causes of aging and cancer. , 1991, Mutation research.

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

[19]  H. Kamiya,et al.  Formation of 2-Hydroxydeoxyadenosine Triphosphate, an Oxidatively Damaged Nucleotide, and Its Incorporation by DNA Polymerases , 1995, The Journal of Biological Chemistry.

[20]  D. Harman,et al.  The aging process. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[21]  H. Harashima,et al.  Dual hydrolysis of diphosphate and triphosphate derivatives of oxidized deoxyadenosine by Orf17 (NtpA), a MutT-type enzyme. , 2005, DNA repair.

[22]  H. Harashima,et al.  Mutagenic effects of 2-hydroxy-dATP on replication in a HeLa extract: induction of substitution and deletion mutations. , 2003, Nucleic acids research.

[23]  K. Sakumi,et al.  Generation and elimination of 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate, a mutagenic substrate for DNA synthesis, in human cells. , 1995, Biochemistry.

[24]  H. Maki,et al.  Hydrolytic elimination of a mutagenic nucleotide, 8-oxodGTP, by human 18-kilodalton protein: sanitization of nucleotide pool. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[25]  H. Harashima,et al.  Hydrolysis of oxidized nucleotides by the Escherichia coli Orf135 protein. , 2001, Biochemical and biophysical research communications.

[26]  H. Harashima,et al.  In vivo mutagenicities of damaged nucleotides produced by nitric oxide and ionizing radiation. , 2005, Biological & pharmaceutical bulletin.

[27]  M. Sekiguchi,et al.  Multiple enzyme activities of Escherichia coli MutT protein for sanitization of DNA and RNA precursor pools. , 2005, Biochemistry.

[28]  K. Yasumoto,et al.  Induction of Chromosomal Gene Mutations in Escherichia coli by Direct Incorporation of Oxidatively Damaged Nucleotides , 1998, The Journal of Biological Chemistry.

[29]  H. Maki,et al.  Two DNA polymerases of Escherichia coli display distinct misinsertion specificities for 2-hydroxy-dATP during DNA synthesis. , 2000, Biochemistry.

[30]  M. Sekiguchi,et al.  Mouse MTH2 protein which prevents mutations caused by 8-oxoguanine nucleotides. , 2003, Biochemical and biophysical research communications.

[31]  J. Tyson McDonald,et al.  Trace amounts of 8-oxo-dGTP in mitochondrial dNTP pools reduce DNA polymerase γ replication fidelity , 2008, Nucleic acids research.

[32]  Yan Xu,et al.  Efficient and erroneous incorporation of oxidized DNA precursors by human DNA polymerase eta. , 2007, Biochemistry.

[33]  H. Harashima,et al.  Mutagenic effects of 8-hydroxy-dGTP in live mammalian cells. , 2007, Free radical biology & medicine.

[34]  H. Kamiya,et al.  Comparison of Oxidation Products from DNA Components by γ-Irradiation and Fenton-Type Reactions , 1997 .

[35]  O. Inanami,et al.  Effects of overexpression and antisense RNA expression of Orf17, a MutT-type enzyme. , 2006, Biological & pharmaceutical bulletin.

[36]  Y. Nakabeppu,et al.  Mutagenic target for hydroxyl radicals generated in Escherichia coli mutant deficient in Mn- and Fe- superoxide dismutases and Fur, a repressor for iron-uptake systems. , 2002, DNA repair.

[37]  F. Hanaoka,et al.  Erroneous incorporation of oxidized DNA precursors by Y‐family DNA polymerases , 2003, EMBO reports.

[38]  M. Sekiguchi,et al.  A novel mechanism for preventing mutations caused by oxidation of guanine nucleotides , 2003, EMBO reports.

[39]  H. Harashima,et al.  Involvement of specialized DNA polymerases in mutagenesis by 8-hydroxy-dGTP in human cells. , 2009, DNA repair.

[40]  H. Harashima,et al.  Roles of specialized DNA polymerases in mutagenesis by 8-hydroxyguanine in human cells. , 2010, Mutation research.

[41]  Y. Nakabeppu,et al.  The Oxidized Forms of dATP Are Substrates for the Human MutT Homologue, the hMTH1 Protein* , 1999, The Journal of Biological Chemistry.

[42]  T Ishikawa,et al.  Spontaneous tumorigenesis in mice defective in the MTH1 gene encoding 8-oxo-dGTPase , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[43]  F. Seela,et al.  Substituent Reactivity and Tautomerism of Isoguanosine and Related Nucleosides , 1995 .

[44]  T. Tsuzuki,et al.  Oxidative nucleotide damage: consequences and prevention , 2002, Oncogene.

[45]  Y. Yamagata,et al.  NUDT5 hydrolyzes oxidized deoxyribonucleoside diphosphates with broad substrate specificity. , 2009, DNA repair.

[46]  D. Frick,et al.  The MutT Proteins or “Nudix” Hydrolases, a Family of Versatile, Widely Distributed, “Housecleaning” Enzymes* , 1996, The Journal of Biological Chemistry.

[47]  H. Maki,et al.  Cloning and expression of cDNA for a human enzyme that hydrolyzes 8-oxo-dGTP, a mutagenic substrate for DNA synthesis. , 1993, The Journal of biological chemistry.

[48]  H. Harashima,et al.  Base excision repair enzyme endonuclease III suppresses mutagenesis caused by 8-hydroxy-dGTP. , 2008, DNA repair.

[49]  D. Shugar,et al.  Tautomerism of Isoguanosine and Solvent-Induced Keto-Enol Equilibrium , 1976, Zeitschrift fur Naturforschung. Section C, Biosciences.

[50]  F. Hanaoka,et al.  2-Hydroxy-2'-deoxyadenosine 5'-triphosphate enhances A.T --> C.G mutations caused by 8-hydroxy-2'-deoxyguanosine 5'-triphosphate by suppressing its degradation upon replication in a HeLa extract. , 2007, Biochemistry.

[51]  H. Harashima,et al.  Increased A:T-->C:G mutations in the mutT strain upon 8-hydroxy-dGTP treatment: direct evidence for MutT involvement in the prevention of mutations by oxidized dGTP. , 2004, Journal of biochemistry.

[52]  C. Kojima,et al.  Amino acid residues involved in substrate recognition of the Escherichia coli Orf135 protein. , 2005, Biochemistry.