PMID:12483507
| Citation |
Sekiguchi, M and Tsuzuki, T (2002) Oxidative nucleotide damage: consequences and prevention. Oncogene 21:8895-904 |
|---|---|
| Abstract |
8-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. |
| Links |
PubMed Online version:10.1038/sj.onc.1206023 |
| Keywords |
Adaptor Proteins, Signal Transducing; Amino Acid Sequence; Animals; Bacterial Proteins/genetics; Bacterial Proteins/metabolism; DNA Damage/physiology; DNA, Bacterial/biosynthesis; Escherichia coli Proteins; Fungal Proteins/genetics; Fungal Proteins/metabolism; Guanine/analogs & derivatives; Guanine/metabolism; Humans; Mammals; Membrane Proteins; Mice; Molecular Sequence Data; Mutagenesis/genetics; Neoplasms, Experimental/genetics; Oxidative Stress; Phosphoric Monoester Hydrolases/genetics; Phosphoric Monoester Hydrolases/metabolism; Pyrophosphatases; Saccharomyces cerevisiae Proteins; Sequence Homology, Amino Acid |
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