Journal Article10.1038/355273A0
Mutt protein specifically hydrolyses a potent mutagenic substrate for dna synthesis
Hisaji Maki,Mutsuo Sekiguchi +1 more
907
TL;DR: A novel mechanism which prevents replicational errors by degrading a potent mutagenic substrate for DNA synthesis is reported, which indicates that elimination from the nucleotide pool of the oxidized form of guanine nucleotide is important for the high fidelity of DNA synthesis.
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Abstract: Errors in the replication of DNA are a major source of spontaneous mutations, and a number of cellular functions are involved in correction of these errors to keep the frequency of spontaneous mutations very low. We report here a novel mechanism which prevents replicational errors by degrading a potent mutagenic substrate for DNA synthesis. This error-avoiding process is catalysed by a protein encoded by the mutT gene of Escherichia coli, mutations of which increase the occurrence of A.T----C.G transversions 100 to 10,000 times the level of the wild type. Spontaneous oxidation of dGTP forms 8-oxo-7,8-dihydro-2'-dGTP (8-oxodGTP), which is inserted opposite dA and dC residues of template DNA with almost equal efficiency, and the MutT protein specifically degrades 8-oxodGTP to the monophosphate. This indicates that elimination from the nucleotide pool of the oxidized form of guanine nucleotide is important for the high fidelity of DNA synthesis.
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Citations
ROS control in human iPS cells reveals early events in spontaneous carcinogenesis.
TL;DR: Results suggest that genes coding for PAX8 and FOSB as well as FGF22, whose expressions are known to increase in developing embryos, may play a pivotal role in cancer formation at the very early stages of cell differentiation.
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Patent
Methods and kits for determing a risk to develop cancer, for evaluating an effectiveness and dosage of cancer therapy and for correlating between an activity of a dna repair enzyme and a cancer
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TL;DR: Methods and kits for determining a risk of a subject to develop cancer, evaluating an effectiveness and dosage of cancer therapy administered to a cancer patient, and determining a presence of correlation or non-correlation between an activity of at least one DNA repair enzyme and at least 1 cancer, are disclosed.
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Combined Ascorbic Acid and Sodium Nitrite Treatment Induces Oxidative DNA Damage-Associated Mutagenicity In Vitro, but Lacks Initiation Activity in Rat Forestomach Epithelium
Yuichi Kuroiwa,Masami Yamada,Keiko Matsui,Toshiya Okamura,Yuji Ishii,Kenichi Masumura,Masako Tasaki,Takashi Umemura,Kunitoshi Mitsumori,Takehiko Nohmi,Masao Hirose,Akiyoshi Nishikawa +11 more
TL;DR: The study indicated that the combination of NaNO(2) with AsA induces genotoxicity due to oxidative DNA damage in vitro, and elevates 8-OHdG levels in the forestomach epithelium, but lacks initiating activity in the rat two-stage carcinogenesis model.
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HMTH1 depletion promotes oxidative-stress-induced apoptosis through a Noxa-and caspase-3/7-mediated signaling pathway
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TL;DR: Data indicate that hMTH1 plays an important role in protecting cells against H(2)O(2)-induced apoptosis via a Noxa- and caspase-3/7-mediated signaling pathway, thus conferring a survival advantage through the inhibition of oxidative-stress-induced DNA damage.
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Functional and structural characterization of DR_0079 from Deinococcus radiodurans, a novel Nudix hydrolase with a preference for cytosine (deoxy)ribonucleoside 5'-Di- and triphosphates.
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