title: Elimination and utilization of oxidized guanine nucleotides in the synthesis of RNA and its precursors.
abstract: Reactive oxygen species are produced as side products of oxygen utilization and can lead to the oxidation of nucleic acids and their precursor nucleotides. Among the various oxidized bases, 8-oxo-7,8-dihydroguanine seems to be the most critical during the transfer of genetic information because it can pair with both cytosine and adenine. During the de novo synthesis of guanine nucleotides, GMP is formed first, and it is converted to GDP by guanylate kinase. This enzyme hardly acts on an oxidized form of GMP (8-oxo-GMP) formed by the oxidation of GMP or by the cleavage of 8-oxo-GDP and 8-oxo-GTP by MutT protein. Although the formation of 8-oxo-GDP from 8-oxo-GMP is thus prevented, 8-oxo-GDP itself may be produced by the oxidation of GDP by reactive oxygen species. The 8-oxo-GDP thus formed can be converted to 8-oxo-GTP because nucleoside-diphosphate kinase and adenylate kinase, both of which catalyze the conversion of GDP to GTP, do not discriminate 8-oxo-GDP from normal GDP. The 8-oxo-GTP produced in this way and by the oxidation of GTP can be used for RNA synthesis. This misincorporation is prevented by MutT protein, which has the potential to cleave 8-oxo-GTP as well as 8-oxo-GDP to 8-oxo-GMP. When (14)C-labeled 8-oxo-GTP was applied to CaCl2-permeabilized cells of a mutT(-) mutant strain, it could be incorporated into RNA at 4% of the rate for GTP. Escherichia coli cells appear to possess mechanisms to prevent misincorporation of 8-oxo-7,8-dihydroguanine into RNA.
authors: Department of Molecular Biology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors: Takeshi
authors: T
authors: Sekiguchi
authors: Department of Biochemistry and Frontier Research Center, Fukuoka Dental College, Fukuoka 814-0193, Japan.
authors: Riyoko
authors: R
authors: Ito
authors: Department of Biochemistry and Frontier Research Center, Fukuoka Dental College, Fukuoka 814-0193, Japan.
authors: Hiroshi
authors: H
authors: Hayakawa
authors: Department of Biochemistry and Frontier Research Center, Fukuoka Dental College, Fukuoka 814-0193, Japan. Electronic address: mseki@college.fdcnet.ac.jp.
authors: Mutsuo
authors: M
authors: Sekiguchi
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000263:Adenylate Kinase / Q000737:chemistry; D003570:Cytidine Triphosphate / Q000737:chemistry; D003848:Deoxyguanine Nucleotides / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry; D006157:Guanosine Monophosphate / Q000737:chemistry; D051528:Guanylate Kinases / Q000737:chemistry; D007700:Kinetics; D009701:Nucleoside-Diphosphate Kinase / Q000737:chemistry; D010084:Oxidation-Reduction; D011755:Pyrophosphatases / Q000737:chemistry; D012329:RNA, Bacterial / Q000096:biosynthesis* / Q000378:metabolism; D014544:Uridine Triphosphate / Q000737:chemistry
chemical_list: D003848:Deoxyguanine Nucleotides; D029968:Escherichia coli Proteins; D012329:RNA, Bacterial; C078206:8-oxodeoxyguanosine triphosphate; D003570:Cytidine Triphosphate; D006157:Guanosine Monophosphate; D000255:Adenosine Triphosphate; D000263:Adenylate Kinase; D009701:Nucleoside-Diphosphate Kinase; D051528:Guanylate Kinases; D011755:Pyrophosphatases; C052211:mutT protein, E coli; D014544:Uridine Triphosphate
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