Caenorhabditis elegans NDX-4 is a MutT-type enzyme that contributes to genomic stability
Caenorhabditis elegans NDX-4 is a MutT-type enzyme that contributes to genomic stability
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DOI：
10.1016/j.dnarep.2010.10.009
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发表时间：
2011-02-07
期刊：
影响因子：
3.8
通讯作者：
Nilsen, Hilde
中科院分区：
文献类型：
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作者：
Arczewska, Katarzyna D.;Baumeier, Christian;Nilsen, Hilde
MutT 酶通过水解 8-oxodGTP（DNA 合成的氧化底物）来防止 DNA 损伤，MutT 酶的抗突变、抗癌和抗神经退行性功能已得到充分证实。 MutT 几乎存在于所有生命王国中，包括许多细菌物种、酵母、植物和哺乳动物。然而，之前并未鉴定出秀丽隐杆线虫 MutT 同源物。在这里，我们证明 NDX-4 具有 MutT 型酶的两个特征，能够水解 8-oxodGTP 并抑制大肠杆菌 mutT 突变体表型。此外，我们表明 NDX-4 有助于线虫体内基因组的稳定性。 ndx-4 突变体的表型分析表明，NDX-4 的缺失会导致关键应激反应基因的上调，这些基因可能补偿 NDX-4 在防止氧化应激的有害后果方面的体内作用。这一发现将使我们能够利用这种极其稳健的遗传模型进一步研究氧化 DNA 损伤对氧化应激相关表型的影响。 (C) 2010 Elsevier B.V. 保留所有权利。
MutT enzymes prevent DNA damage by hydrolysis of 8-oxodGTP, an oxidized substrate for DNA synthesis and antimutagenic, anticarcinogenic, and antineurodegenerative functions of MutT enzymes are well established. MutT has been found in almost all kingdoms of life, including many bacterial species, yeasts, plants and mammals. However, a Caenorhabditis elegans MutT homologue was not previously identified. Here, we demonstrate that NDX-4 exhibits both hallmarks of a MutT-type enzyme with an ability to hydrolyze 8-oxodGTP and suppress the Escherichia coli mutT mutator phenotype. Moreover, we show that NDX-4 contributes to genomic stability in vivo in C. elegans. Phenotypic analyses of an ndx-4 mutant reveal that loss of NDX-4 leads to upregulation of key stress responsive genes that likely compensate for the in vivo role of NDX-4 in protection against deleterious consequences of oxidative stress. This discovery will enable us to use this extremely robust genetic model for further research into the contribution of oxidative DNA damage to phenotypes associated with oxidative stress. (C) 2010 Elsevier B.V. All rights reserved.