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lüll Oxidative nucleotide damage: consequences and prevention Sekiguchi M; Tsuzuki TOncogene 2002[Dec]; 21 (58): 8895-9048-Oxoguanine (8-oxo-7,8-dihydroguanine) is produced in DNA, as well as in nucleotide pools of cells, by reactive oxygen species normally formed during cellular metabolic processes. 8-Oxoguanine nucleotide can pair with cytosine and adenine nucleotides with an almost equal efficiency, then transversion mutation ensues. MutT protein of Escherichia coli and related mammalian protein MTH1 specifically degrade 8-oxo-dGTP to 8-oxo-dGMP, thereby preventing misincorporation of 8-oxoguanine into DNA. The bacterial and mammalian enzymes are close in their size and share a highly conserved region consisting of 23 residues with 14 identical amino acids. Following saturation mutagenesis of this region, most of these residues proved to be essential to exert 8-oxo-dGTPase activity. Gene targeting was done to establish MTH1-deficient cell lines and mice for study. When examined 18 months after birth, a greater number of tumors were formed in the lungs, livers, and stomachs of MTH1(-/-) mice, as compared with findings in wild-type mice. These proteins protect genetic information from untoward effects of threats of endogenous oxygen.|*Escherichia coli Proteins[MESH]|*Membrane Proteins[MESH]|*Saccharomyces cerevisiae Proteins[MESH]|Adaptor Proteins, Signal Transducing[MESH]|Amino Acid Sequence[MESH]|Animals[MESH]|Bacterial Proteins/genetics/*metabolism[MESH]|DNA Damage/*physiology[MESH]|DNA, Bacterial/biosynthesis[MESH]|Fungal Proteins/genetics/*metabolism[MESH]|Guanine/*analogs & derivatives/*metabolism[MESH]|Humans[MESH]|Mammals[MESH]|Mice[MESH]|Molecular Sequence Data[MESH]|Mutagenesis/genetics[MESH]|Neoplasms, Experimental/genetics[MESH]|Oxidative Stress[MESH]|Phosphoric Monoester Hydrolases/genetics/*metabolism[MESH]|Pyrophosphatases[MESH]|Sequence Homology, Amino Acid[MESH] |