Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Free Radic Biol Med. 2010 May 1;48(9):1197-201. doi: 10.1016/j.freeradbiomed.2010.02.002. Epub 2010 Feb 6.
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.
为了评估三种人类 MutT 型酶（MTH1、MTH2 和 NUDT5）的功能，我们使用经过特定 siRNA 处理的人 293T 细胞，研究了氧化形式的 dGTP（8-羟基-2'-脱氧鸟苷 5'-三磷酸（8-OH-dGTP；7,8-二氢-8-氧代-2'-脱氧鸟苷 5'-三磷酸）诱导的突变。首先将含有 supF 基因的穿梭质粒 DNA 转染到细胞中，然后通过渗透压引入 8-OH-dGTP。用在处理过的细胞中复制的 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 取代突变。此外，三重敲低细胞中诱导的突变频率增加更为明显。这些结果表明，人类 MTH1、MTH2 和 NUDT5 蛋白均能抵御氧化 dGTP 诱导的致突变作用。
DNA Repair (Amst). 2009-5-1
Nucleic Acids Res. 2024-6-24
Free Radic Biol Med. 2007-5-15
Transl Cancer Res. 2025-7-30
Nucleic Acids Res. 2024-6-24
Breast Cancer Res. 2024-2-5
Nat Chem Biol. 2020-7-20
Bioinformation. 2019-12-5
Ther Adv Med Oncol. 2019-8-23
Zotero 插件