Molecular cloning and functional expression of a human cDNA encoding the antimutator enzyme 8-hydroxyguanine-DNA glycosylase
Molecular cloning and functional expression of a human cDNA encoding the antimutator enzyme 8-hydroxyguanine-DNA glycosylase
复制标题
DOI：
10.1073/pnas.94.15.8016
复制
发表时间：
1997-07-22
影响因子：
11.1
通讯作者：
Lindahl, T
中科院分区：
文献类型：
--
作者：
RoldanArjona, T;Wei, YF;Lindahl, T
由暴露于活性氧引起的DNA中的主要致突变碱基损伤是8-羟基鸟嘌呤（8-氧代-7，8-二氢鸟嘌呤）。在细菌和酿酒酵母中，这种受损碱基被具有相关裂解酶活性的DNA糖基化酶切除，用于链裂解。我们克隆、测序并表达了一个与酵母相关基因具有部分同源性的人cDNA，编码的47-kDa人酶从氧化DNA中释放游离的8-羟基鸟嘌呤，并在双链寡核苷酸中特异性地在与胞嘧啶配对的8-羟基鸟嘌呤残基碱基处引入链断裂。coli mutM mutY菌株部分抑制其自发突变表型。编码人类酶的基因定位于染色体3 p25。这些结果表明，人类细胞具有一种酶，该酶可以在由活性氧引起的诱变DNA损伤处启动碱基切除修复。
The major mutagenic base lesion in DNA caused by exposure to reactive oxygen species is 8-hydroxyguanine (8-oxo-7,8-dihydroguanine), In bacteria and Saccharomyces cerevisiae, this damaged base is excised by a DNA glycosylase with an associated lyase activity for chain cleavage. We have cloned, sequenced, and expressed a human cDNA with partial sequence homology to the relevant yeast gene, The encoded 47-kDa human enzyme releases free 8-hydroxyguanine from oxidized DNA and introduces a chain break in a double-stranded oligonucleotide specifically at an 8-hydroxyguanine residue base paired with cytosine, Expression of the human protein in a DNA repair-deficient E. coli mutM mutY strain partly suppresses its spontaneous mutator phenotype. The gene encoding the human enzyme maps to chromosome 3p25. These results show that human cells have an enzyme that fan initiate base excision repair at mutagenic DNA lesions caused by active oxygen.