Reactome | NUDT1 hydrolyses 8-oxo-dGTP to 8-oxo-dGMP

NUDT1 hydrolyses 8-oxo-dGTP to 8-oxo-dGMP

Stable Identifier

R-HSA-2395849

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

Synonyms

8-oxo-dGTP + H2O => 8-oxo-dGMP + PPi (NUDT1)

ReviewStatus

5/5

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NUDT1 hydrolyses 8-oxo-dGTP to 8-oxo-dGMP

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NUDT1 (MTH1) catalyzes the reaction of 8-oxo-dGTP and water to form 8-oxo-dGMP and PPi (pyrophosphate). Four NUDT1 proteins have been identified, encoded by a single gene with alternative start codons (Oda et al. 1999). The shortest of these, NUDT1 p18, has been biochemically (Sakumi et al. 1993; Takagi et al. 2012) and structurally (Mishima et al. 2004) characterized and shown to catalyze hydrolysis of 8-oxo-dGTP. The active enzyme is a monomer associated with a magnesium ion (Mishima et al. 2004). The longer isoforms all consist of the p18 polypeptide with aminoterminal extensions and are presumed to be active as well but have not been experimentally characterized. The p18 isoform is predominantly cytosolic (Kang et al. 1995). Its expression prevents the accumulation of oxo-guanine bases in DNA in mutant mouse cells lacking endogenous NUDT1 activity (Yoshimura et al. 2003).

Together, these data support the hypothesis that by cleaving 8-oxo-dGTP and thus preventing its incorporation into DNA NUDT1 provides a physiologically important defense against mutagenesis due to oxidative stress.

Literature References

PubMed ID	Title	Journal	Year
15133035	Structure of human MTH1, a Nudix family hydrolase that selectively degrades oxidized purine nucleoside triphosphates Mishima, M, Shirakawa, M, Itoh, N, Takahashi, M, Furuichi, M, Iwai, S, Nakabeppu, Y, Yamagata, Y, Sakai, Y, Kamiya, H	J. Biol. Chem.	2004
12857738	An oxidized purine nucleoside triphosphatase, MTH1, suppresses cell death caused by oxidative stress Furuichi, M, Yoshimura, D, Iwai, S, Ohno, M, Nakabeppu, Y, Sakumi, K, Sakai, Y	J. Biol. Chem.	2003
22556419	Human MTH3 (NUDT18) Protein Hydrolyzes Oxidized Forms of Guanosine and Deoxyguanosine Diphosphates: COMPARISON WITH MTH1 AND MTH2 Takagi, Y, Ito, R, Sekiguchi, M, Yamagata, Y, Setoyama, D, Kamiya, H	J. Biol. Chem.	2012
10536140	Multi-forms of human MTH1 polypeptides produced by alternative translation initiation and single nucleotide polymorphism Itoh, R, Nishioka, K, Oda, H, Taketomi, A, Suzuki, T, Maruyama, R, Nakabeppu, Y, Sekiguchi, M, Yakushiji, H	Nucleic Acids Res.	1999
7782328	Intracellular localization of 8-oxo-dGTPase in human cells, with special reference to the role of the enzyme in mitochondria Iyama, A, Furuichi, M, Fujiwara, T, Nishida, J, Nakabeppu, Y, Kang, D, Sekiguchi, M, Takeshige, K	J. Biol. Chem.	1995
8226881	Cloning and expression of cDNA for a human enzyme that hydrolyzes 8-oxo-dGTP, a mutagenic substrate for DNA synthesis Tsuzuki, T, Kakuma, T, Furuichi, M, Maki, H, Kawabata, S, Sekiguchi, M, Sakumi, K	J. Biol. Chem.	1993