| First Author | Sekiguchi M | Year | 2002 |
| Journal | Oncogene | Volume | 21 |
| Issue | 58 | Pages | 8895-904 |
| PubMed ID | 12483507 | Mgi Jnum | J:81237 |
| Mgi Id | MGI:2448402 | Doi | 10.1038/sj.onc.1206023 |
| Citation | Sekiguchi M, et al. (2002) Oxidative nucleotide damage: consequences and prevention. Oncogene 21(58):8895-904 |
| abstractText | 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. |
