Translesional synthesis on DNA templates containing an estrogen quinone-derived adduct: N2-(2-hydroxyestron-6-yl)-2'-deoxyguanosine and N6-(2-hydroxyestron-6-yl)-2'-deoxyadenosine.
Translesional synthesis on DNA templates containing an estrogen quinone-derived adduct: N2-(2-hydroxyestron-6-yl)-2'-deoxyguanosine and N6-(2-hydroxyestron-6-yl)-2'-deoxyadenosine.
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在含有雌激素醌衍生加合物的 DNA 模板上进行跨病灶合成：N2-(2-羟基雌酮-6-基)-2-脱氧鸟苷和 N6-(2-羟基雌酮-6-基)-2-脱氧腺苷。
DOI：
10.1021/bi981235e
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发表时间：
1998
期刊：
影响因子：
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通讯作者：
Shibutani,S
中科院分区：
文献类型：
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作者：
Terashima,I;Suzuki,N;Dasaradhi,L;Tan,CK;Downey,KM;Shibutani,S
雌激素醌衍生的DNA加合物诱导的错误编码的性质进行了分析，使用在体外实验系统，以量化碱基替换和缺失。合成后制备了含有N2-（2-羟基雌酮-6-基）-2 '-脱氧鸟苷（2-OHE 1-N2-dG）或N6-（2-羟基雌酮-6-基）-2'-脱氧腺苷（2-OHE 1-N6-dA）的位点特异性修饰的寡核苷酸，并将其用作哺乳动物DNA聚合酶（pol）α、β和δ催化的引物延伸反应的模板。2-OHE 1-N2-dG加合物比2-OHE 1-N6-dA更强地阻断引物延伸反应。使用pol α和δ，2-OHE 1-N2-dG促进dCMP（分别为6.3%和3.1%）的掺入，dCMP是正确的碱基，与损伤相对：当使用pol δ时，检测到dTMP的错误掺入（0.52%）。2-OHE 1-N6-dA也促进了dTMP（正确碱基）的掺入，并伴随着dCTP的错误掺入（pol α为0.54%，pol δ为3.2%）和一个碱基缺失（0.3 - 0.5%）。使用pol β，未检测到错误编码。只有当使用复制型DNA聚合酶时才发生错误编码。动力学数据与分析pol α或pol β形成的完全延伸产物所得数据一致。这些结果表明，内源性雌激素醌衍生的DNA加合物具有错误编码的可能性：在哺乳动物细胞中预测G → A和A → G转换和缺失。
Miscoding properties induced by estrogen quinone-derived DNA adducts were analyzed using an in vitro experimental system to quantify base substitutions and deletions. Site-specifically modified oligodeoxynucleotides containing a singleN2-(2-hydroxyestron-6-yl)-2‘-deoxyguanosine (2-OHE1-N2-dG) orN6-(2-hydroxyestron-6-yl)-2‘-deoxyadenosine (2-OHE1-N6-dA) were prepared postsynthetically and used as templates in primer extension reactions catalyzed by mammalian DNA polymerases (pol) α, β, and δ. The 2-OHE1-N2-dG adduct blocked primer extension reactions more strongly than 2-OHE1-N6-dA. Using pol α and δ, 2-OHE1-N2-dG promoted incorporation of dCMP (6.3 and 3.1%, respectively), the correct base, opposite the lesion: when pol δ was used, misincorporation of dTMP (0.52%) was detected. 2-OHE1-N6-dA also promoted incorporation of dTMP, the correct base, opposite the lesion, accompanied by misincorporation of dCTP (0.54% for pol α and 3.2% for pol δ) and one-base deletion (0.3−0.5%). Using pol β, no miscoding was detected. The miscoding occurred only when replicative DNA polymerases were used. Kinetic data were consistent with those obtained from the analysis of fully extended products formed by pol α or pol β. These results indicate that endogenous estrogen quinone-derived DNA adducts have miscoding potential: G → A and A → G transitions and deletions are predicted in mammalian cells.