Suppression of mutagenesis by 8-hydroxy-2′-deoxyguanosine 5′-triphosphate (7,8-dihydro-8-oxo-2′-deoxyguanosine 5′-triphosphate) by human MTH1, MTH2, and NUDT5
Suppression of mutagenesis by 8-hydroxy-2′-deoxyguanosine 5′-triphosphate (7,8-dihydro-8-oxo-2′-deoxyguanosine 5′-triphosphate) by human MTH1, MTH2, and NUDT5
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DOI：
10.1016/j.freeradbiomed.2010.02.002
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发表时间：
2010-05-01
影响因子：
7.4
通讯作者：
Kamiya, Hiroyuki
中科院分区：
文献类型：
--
作者：
Hori, Mika;Satou, Kazuya;Kamiya, Hiroyuki
为了评估三种人mutt型酶MTH1、MTH2和NUDT5的功能，我们使用经过特异性sirna处理的人293T细胞，检测了氧化形式dGTP 8- oh -2'-脱氧鸟苷5'-三磷酸（8-OH-dGTP; 7,8-二氢-8-氧-2'-脱氧鸟苷5'-三磷酸）诱导突变的情况。首先将含有supF基因的穿梭质粒DNA转染到细胞中，然后通过渗透压法导入8-OH-dGTP。用在处理细胞中复制的dna转化大肠杆菌细胞。MTH1、MTH2和NUDT5蛋白的敲低增加了8-OH-dGTP诱导的A:T -> C:G替代突变。此外，在三敲低的细胞中，诱导突变频率的增加更为明显。这些结果表明，所有三种人类MTH1， MTH2和NUDT5蛋白都可以防御氧化dGTP诱导的突变。(C) 2010爱思唯尔公司版权所有。
To assess the functions of the three human MutT-type enzymes, MTH1, MTH2, and NUDT5, mutation induction by an oxidized form of dGTP, 8-hydroxy-2'-deoxyguanosine 5'-triphosphate (8-OH-dGTP; 7,8-dihydro-8-oxo-2'-deoxyguanosine 5'-triphosphate), was examined using human 293T cells treated with their specific siRNAs. Shuttle plasmid DNA containing the supF gene was first transfected into the cells, and then 8-OH-dGTP was introduced by means of osmotic pressure. Escherichia coli cells were transformed with the DNAs replicated in the treated cells. The knockdown of the MTH1, MTH2, and NUDT5 proteins increased the A:T -> C:G substitution mutations induced by 8-OH-dGTP. In addition, the increase in the induced mutation frequency was more evident in the triple-knockdown cells. These results indicate that all three of the human MTH1, MTH2, and NUDT5 proteins act as a defense against the mutagenesis induced by oxidized dGTP. (C) 2010 Elsevier Inc. All rights reserved.