Mammalian enzymes for preventing transcriptional errors caused by oxidative damage.
Mammalian enzymes for preventing transcriptional errors caused by oxidative damage.
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DOI：
10.1093/nar/gki682
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发表时间：
2005
影响因子：
14.9
通讯作者：
Sekiguchi M
中科院分区：
文献类型：
--
作者：
Ishibashi T;Hayakawa H;Ito R;Miyazawa M;Yamagata Y;Sekiguchi M
8-氧代-7，8-二氢鸟嘌呤（8-oxoGua）是由细胞代谢过程中正常形成的活性氧在细胞中产生的。这种氧化的碱基可以与腺嘌呤和胞嘧啶配对，因此信使RNA中这种碱基的存在会导致翻译错误。大肠杆菌的MutT蛋白将含有8-oxoGua的核糖核苷二磷酸和三磷酸降解为单磷酸，从而防止8-oxoGua错误掺入RNA中。在这里，我们表明，对于人类的MutT相关蛋白，NUDT 5和MTH 1有能力防止氧化损伤引起的翻译错误。在大肠杆菌mutT缺陷细胞中，由氧化损伤引起的错误蛋白质的产生增加是野生型细胞的28倍。通过在细胞中表达NUDT 5或MTH 1，其分别降低至1.4或1.2倍。NUDT 5和MTH 1将8-oxoGDP水解为8-oxoGMP，Vmax/Km值分别为1.3 × 10−3和1.7 × 10−3，显著高于其正常对应物GDP（0.1-0.5 × 10−3）。MTH 1而非NUDT 5具有将8-oxoGTP降解为单磷酸的额外活性。这些结果表明，从前体库中消除含有8-氧代Gua的核糖核苷酸对于确保准确的蛋白质合成是重要的，并且NUDT 5和MTH 1都参与了人类细胞中的这一过程。
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 × 10−3 and 1.7 × 10−3, respectively, values which are considerably higher than those for its normal counterpart, GDP (0.1–0.5 × 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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影响因子：
2.9
作者：
Ito, R;Hayakawa, H;Ishibashi, T
通讯作者：
Ishibashi, T
影响因子：
4.8
作者：
Fujikawa, K;Kamiya, H;Kasai, H
通讯作者：
Kasai, H
影响因子：
4.7
作者：
KASAI, H;CRAIN, PF;TANOOKA, H
通讯作者：
TANOOKA, H
影响因子：
8
作者：
Sekiguchi, M;Tsuzuki, T
通讯作者：
Tsuzuki, T
DOI：
10.1073/pnas.89.15.7022
发表时间：
1992-08-01
影响因子：
11.1
作者：
MICHAELS, ML;CRUZ, C;MILLER, JH
通讯作者：
MILLER, JH