MUTT PROTEIN SPECIFICALLY HYDROLYZES A POTENT MUTAGENIC SUBSTRATE FOR DNA-SYNTHESIS
MUTT PROTEIN SPECIFICALLY HYDROLYZES A POTENT MUTAGENIC SUBSTRATE FOR DNA-SYNTHESIS
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DOI：
10.1038/355273a0
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发表时间：
1992-01-16
期刊：
影响因子：
64.8
通讯作者：
SEKIGUCHI, M
中科院分区：
文献类型：
--
作者：
MAKI, H;SEKIGUCHI, M
DNA复制中的错误是自发突变的主要来源，许多细胞功能参与了这些错误的纠正，以保持自发突变的频率非常低。我们在这里报告了一种新的机制，通过降解DNA合成的强诱变底物来防止复制错误。这种避免错误的过程是由大肠杆菌mutT基因编码的蛋白质催化的，该基因的突变会增加a的发生。T——b> c。G转换是野生型2的100到10000倍。dGTP的自发氧化形成8-oxo-7,8-二氢-2'-dGTP (8-oxodGTP)，以几乎相同的效率插入模板DNA的dA和dC残基的相反位置，MutT蛋白特异性地将8-oxodGTP降解为单磷酸。这表明从核苷酸池中清除氧化形式的鸟嘌呤核苷酸对DNA合成的高保真度很重要。
ERRORS in the replication of DNA are a major source of spontaneous mutations, and a number of cellular functions are involved in correction of these errors to keep the frequency of spontaneous mutations very low 1. We report here a novel mechanism which prevents replicational errors by degrading a potent mutagenic substrate for DNA synthesis. This error-avoiding process is catalysed by a protein encoded by the mutT gene of Escherichia coli, mutations of which increase the occurrence of A . T --> C . G transversions 100 to 10,000 times the level of the wild type 2. Spontaneous oxidation of dGTP forms 8-oxo-7,8-dihydro-2'-dGTP (8-oxodGTP), which is inserted opposite dA and dC residues of template DNA with almost equal efficiency, and the MutT protein specifically degrades 8-oxodGTP to the monophosphate. This indicates that elimination from the nucleotide pool of the oxidized form of guanine nucleotide is important for the high fidelity of DNA synthesis.