Programmed cell death triggered by nucleotide pool damage and its prevention by MutT homolog-1 (MTH1) with oxidized purine nucleoside triphosphatase.
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.
Nakabeppu
Yusaku
Y
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. yusaku@bioreg.kyushu-u.ac.jp
Oka
Sugako
S
Sheng
Zijing
Z
Tsuchimoto
Daisuke
D
Sakumi
Kunihiko
K
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D004249:DNA Damage; D045643:DNA Repair Enzymes / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000378:metabolism; D003848:Deoxyguanine Nucleotides / Q000378:metabolism*; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D009410:Nerve Degeneration; D009474:Neurons / Q000378:metabolism; D043583:Nucleoside-Triphosphatase / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011684:Purine Nucleosides / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
C095141:2-hydroxydeoxyadenosine triphosphate; D004272:DNA, Mitochondrial; D003848:Deoxyguanine Nucleotides; D011684:Purine Nucleosides; D017382:Reactive Oxygen Species; C078206:8-oxodeoxyguanosine triphosphate; C024829:8-hydroxyguanine; D006147:Guanine; D000255:Adenosine Triphosphate; D010744:Phosphoric Monoester Hydrolases; D043583:Nucleoside-Triphosphatase; C078207:8-oxodGTPase; D045643:DNA Repair Enzymes