Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Mutat Res. 2010 Nov 28;703(1):51-8. doi: 10.1016/j.mrgentox.2010.06.006. Epub 2010 Jun 11.
Accumulation of oxidized bases such as 8-oxoguanine in either nuclear or mitochondrial DNA triggers various cellular dysfunctions including mutagenesis, and programmed cell death or senescence. Recent studies have revealed that oxidized nucleoside triphosphates such as 8-oxo-dGTP in the nucleotide pool are the main source of oxidized bases accumulating in the DNA of cells under oxidative stress. To counteract such deleterious effects of nucleotide pool damage, mammalian cells possess MutT homolog-1 (MTH1) with oxidized purine nucleoside triphosphatase and related enzymes, thus minimizing the accumulation of oxidized bases in cellular DNA. Depletion or increased expression of the MTH1 protein have revealed its significant roles in avoiding programmed cell death or senescence as well as mutagenesis, and accumulating evidences indicate that MTH1 is involved in suppression of degenerative disorders such as neurodegeneration.
氧化碱基（如 8-氧鸟嘌呤）在核或线粒体 DNA 中的积累会引发各种细胞功能障碍，包括突变、程序性细胞死亡或衰老。最近的研究表明，核苷酸池中的氧化核苷三磷酸（如氧化型 dGTP）是氧化应激下细胞 DNA 中积累的氧化碱基的主要来源。为了抵消核苷酸池损伤的这种有害影响，哺乳动物细胞具有具有氧化嘌呤核苷三磷酸酶和相关酶的 MutT 同源物-1（MTH1），从而最大限度地减少细胞 DNA 中氧化碱基的积累。MTH1 蛋白的耗竭或表达增加揭示了其在避免程序性细胞死亡或衰老以及突变中的重要作用，越来越多的证据表明 MTH1 参与抑制神经退行性疾病等退行性疾病。
