Stability, miscoding potential, and repair of 2'-deoxyxanthosine in DNA: implications for nitric oxide-induced mutagenesis.
Stability, miscoding potential, and repair of 2'-deoxyxanthosine in DNA: implications for nitric oxide-induced mutagenesis.
复制标题
DNA 中 2-脱氧黄苷的稳定性、错误编码潜力和修复：对一氧化氮诱导突变的影响。
DOI：
10.1021/bi0205597
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Termini,John
中科院分区：
文献类型：
--
作者：
Wuenschell,GeraldE;O'Connor,TimothyR;Termini,John
Nitric oxide (NO•) reacts with guanine in DNA and RNA to produce xanthine (X) as a major product. Despite its potential importance in NO•-mediated mutagenesis, the biochemical properties of X in polynucleotides have been relatively unexplored. We describe the synthesis and chemical characterization of xanthine-containing oligonucleotides and report on the susceptibility of X to depurination, its miscoding potential during replication by polymerases, and its recognition and excision by several members of the base excision repair (BER) family of DNA glycosylases. At neutral pH, X was found to be only slightly less stable than guanine to depurination (kX/kG= 1.19), whereas at pH ≤ 4 the depurination rate exceeded that of G by more than an order of magnitude. HIV-1 RT inserted dCTP and dTTP with approximately equal frequencies opposite X in a DNA template, whereas DNA Pol 1(KF-) preferentially inserted dCTP. Several DNA glycosylases were found to excise X specifically in X·C base pairs, whereas activity toward X·G, X·A, or X·T pairs was detected only for AlkA. The order of reactivity of glycosylases for the removal of X·C base pairs was found to be AlkA > Mpg > Nth > Fpg. Implications of these results for the induction of mutations by nitric oxide are discussed.
