Sequence preference of 7,12-dimethylbenz[a]anthracene-syn-diol epoxide-DNA binding in the mouse H-ras gene detected by UvrABC nucleases.
Sequence preference of 7,12-dimethylbenz[a]anthracene-syn-diol epoxide-DNA binding in the mouse H-ras gene detected by UvrABC nucleases.
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UvrABC 核酸酶检测小鼠 H-ras 基因中 7,12-二甲基苯并[a]蒽-syn-二醇环氧化物-DNA 结合的序列偏好。
DOI：
10.1021/bi9604136
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Tang,MS
中科院分区：
文献类型：
--
作者：
Chen,JX;Pao,A;Zheng,Y;Ye,X;Kisleyou,AS;Morris,R;Slaga,TJ;Harvey,RG;Tang,MS
我们已经发现7，12-二甲基苯并[a]蒽-顺-二醇环氧化物（syn-DMBADE）修饰的DNA片段对UVrABC切割敏感。切口主要发生在5 ′端的7个碱基和3 ′端的4个碱基上，它们是由腺嘌呤或鸟嘌呤残基修饰的。DNA片段中不同序列的UvrABC切割动力学是相同的，并且UvrABC切割的程度与syn-DMBADE浓度成正比。基于这些结果，我们得出结论，UvrABC对syn-DMBADE − DNA加合物的切割与DNA序列无关，并且是定量的。使用UvrABC切割方法，我们分析了几个定义的DNA片段中的thesyn-DMBADE − DNA结合谱，包括小鼠H-ras基因的前两个外显子。我们发现H-ras基因密码子12、13和61的鸟嘌呤和腺嘌呤残基都是强的syn-DMBADE结合位点。这些结果表明，DMBADE的初始结合可能大大有助于H-ras突变的频率。二核苷酸结合分析的结果表明，5'-最近邻对syn-DMBADE − DNA结合的影响大于3'-最近邻。
We have found that 7,12-dimethylbenz[a]anthracene-syn-diol epoxide (syn-DMBADE)-modified DNA fragments are sensitive to UvrABC incision. The incisions occur mainly seven bases 5‘ and four bases 3‘ of asyn-DMBADE-modified adenine or guanine residue. The kinetics of UvrABC incision at different sequences in a DNA fragment are the same, and the extent of UvrABC incision is proportional to thesyn-DMBADE concentration. On the basis of these results, we have concluded that UvrABC incision onsyn-DMBADE−DNA adducts is independent of DNA sequence and is quantitative. Using the UvrABC incision method, we have analyzed thesyn-DMBADE−DNA binding spectrum in several defined DNA fragments, including the first two exons of the mouse H-rasgene. We have found that both guanine and adenine residues in codons 12, 13, and 61 of the H-rasgene are strongsyn-DMBADE binding sites. These results suggest that the initial binding of DMBADE may greatly contribute to the frequency of H-rasmutations. Results from dinucleotide binding analysis indicate that the 5‘-nearest neighbor displays a greater effect onsyn-DMBADE−DNA binding than the 3‘-nearest neighbor.