期刊
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
卷 703, 期 1, 页码 51-58出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.mrgentox.2010.06.006
关键词
8-Oxo-dGTP; 2-OH-dATP; Nucleotide pool; MTH1; OCG1; MUTYH; Programmed cell death
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [20013034, 20012038]
- Japan Society for the Promotion of Science [19390114]
- Kyushu University
- Grants-in-Aid for Scientific Research [20012038, 19390114, 20013034] Funding Source: KAKEN
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 ut 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 till 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 de generative disorders such as neurodegeneration. (C) 2010 Elsevier B.V. All rights reserved.
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