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Nucleic Acids Research 2005 33(12):3779-3784; doi:10.1093/nar/gki682
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Published online 7 July 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions{at}oupjournals.org

Article

Mammalian enzymes for preventing transcriptional errors caused by oxidative damage

Toru Ishibashi1,2,*, Hiroshi Hayakawa3, Riyoko Ito2, Masayuki Miyazawa4, Yuriko Yamagata4 and Mutsuo Sekiguchi1,2

1Biomolecular Engineering Research Institute Suita, Osaka 565-0874, Japan 2Department of Physiological Science and Molecular Biology and Frontier Research Center, Fukuoka Dental College Fukuoka 814-0193, Japan 3Department of Medical Biochemistry, Graduate School of Medical Science, Kyushu University Fukuoka 812-8582, Japan 4Graduate School of Pharmaceutical Sciences, Kumamoto University Kumamoto 862-0973, Japan

*To whom correspondence should be addressed. Tel: +81 6 6872 8200; Fax: +81 6 6872 8210; Email: toruishi{at}beri.or.jp

Received March 31, 2005. Revised June 13, 2005. Accepted June 13, 2005.

8-Oxo-7,8-dihydroguanine (8-oxoGua) is produced in cells by reactive oxygen species normally formed during cellular metabolic processes. This oxidized base can pair with both adenine and cytosine, and thus the existence of this base in messenger RNA would cause translational errors. The MutT protein of Escherichia coli degrades 8-oxoGua-containing ribonucleoside di- and triphosphates to the monophosphate, thereby preventing the misincorporation of 8-oxoGua into RNA. Here, we show that for human the MutT-related proteins, NUDT5 and MTH1 have the ability to prevent translational errors caused by oxidative damage. The increase in the production of erroneous proteins by oxidative damage is 28-fold over the wild-type cells in E.coli mutT deficient cells. By the expression of NUDT5 or MTH1 in the cells, it is reduced to 1.4- or 1.2-fold, respectively. NUDT5 and MTH1 hydrolyze 8-oxoGDP to 8-oxoGMP with Vmax/Km values of 1.3 x 10–3 and 1.7 x 10–3, respectively, values which are considerably higher than those for its normal counterpart, GDP (0.1–0.5 x 10–3). MTH1, but not NUDT5, possesses an additional activity to degrade 8-oxoGTP to the monophosphate. These results indicate that the elimination of 8-oxoGua-containing ribonucleotides from the precursor pool is important to ensure accurate protein synthesis and that both NUDT5 and MTH1 are involved in this process in human cells.


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 Plant Cell PhysiolHome page
K. Yoshimura, T. Ogawa, Y. Ueda, and S. Shigeoka
AtNUDX1, an 8-Oxo-7,8-Dihydro-2'-Deoxyguanosine 5'-Triphosphate Pyrophosphohydrolase, is Responsible for Eliminating Oxidized Nucleotides in Arabidopsis
Plant Cell Physiol., October 1, 2007; 48(10): 1438 - 1449.
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