Iwai Shigenori, Inase Aki, Jafar Sharif, Higurashi Miho, Ohtsuki Takashi, Xu Yan, Sugiyama Hiroshi
Division of Chemistry, Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531, Japan.
Nucleic Acids Res Suppl. 2003(3):181-2. doi: 10.1093/nass/3.1.181.
Properties of the DNA containing the (6-4) photoproduct, one of the major UV-induced lesions, were analyzed. Two basic studies towards artificial recognition and repair of this type of damaged DNA are presented here. One is recognition of the UV-damaged DNA by a minor groove-binding drug. It was found by CD spectroscopy that distamycin could bind DNA duplexes containing the (6-4) photoproduct as effectively as the unmodified DNA, whereas a DNA duplex containing the cyclobutane pyrimidine dimer was not recognized by this drug. The other is a mechanistic study on alkali degradation of this photoproduct. HPLC and NMR analyses revealed that hydrolysis between the N3 and C4 positions of the 5' pyrimidine component occurred first. This intermediate was relatively stable, and further degradation to the strand break required severe conditions like the hot piperidine treatment.
对含有（6-4）光产物（紫外线诱导产生的主要损伤之一）的DNA特性进行了分析。本文介绍了针对此类受损DNA进行人工识别和修复的两项基础研究。一是通过一种小沟结合药物识别紫外线损伤的DNA。通过圆二色光谱法发现，偏端霉素能够与含有（6-4）光产物的DNA双链体有效结合，其效果与未修饰的DNA相同，而含有环丁烷嘧啶二聚体的DNA双链体则不能被这种药物识别。另一个是对这种光产物碱降解的机理研究。高效液相色谱和核磁共振分析表明，5'嘧啶成分的N3和C4位置之间首先发生水解。这种中间体相对稳定，进一步降解为链断裂需要如热哌啶处理等严苛条件。
