DNA structural reorganization upon conversion of a psoralen furan-side monoadduct to an interstrand cross-link: implications for DNA repair.
DNA structural reorganization upon conversion of a psoralen furan-side monoadduct to an interstrand cross-link: implications for DNA repair.
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补骨脂素呋喃侧单加合物转化为链间交联后的 DNA 结构重组：对 DNA 修复的影响。
DOI：
10.1073/pnas.92.6.2345
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发表时间：
1995
影响因子：
11.1
通讯作者：
Wemmer,DE
中科院分区：
文献类型：
--
作者：
Spielmann,HP;Dwyer,TJ;Sastry,SS;Hearst,JE;Wemmer,DE
我们利用1H NMR谱测定了DNA低聚物d(5'-GCGTACGC-3')2在4'-羟基甲基-4,5'，8-三甲基补骨脂-DNA呋喃侧单加合物（MAf）转化为链间交联（XL）时所引起的结构变化。MAf是通向XL链的光化学中间体，其补骨脂素嵌入螺旋结构中。两种加合物的局部DNA结构都是扭曲的，但在三个碱基对内恢复正常。XL的形成需要补骨脂素向最初未修饰的链移动，伴随着胸腺嘧啶C-5和C-6碳的杂交变化以及局部螺旋扭曲的变化。MAf嵌入在螺旋中。在MAf或XL的螺旋轴上没有明显的弯曲。在光加合物形成过程中，局部螺旋动力学的显著变化可能被细胞DNA修复酶系统识别。我们假设修复酶通过检测dna损伤剂诱导的糖-磷酸骨架的构象灵活性来靶向病变。
We have used 1H NMR spectroscopy to determine the structural changes induced in the DNA oligomer d(5'-GCGTACGC-3')2 upon conversion of the 4'-hydroxy-methyl-4,5',8-trimethylpsoralen-DNA furan-side monoadduct (MAf) to the interstrand cross-link (XL). The MAf is a photochemical intermediate on the path to interstrand XL and has the psoralen intercalated into the helix. The local DNA structure is distorted in both adducts, but it returns to normal within three base pairs. The formation of XL requires displacement of the psoralen toward the initially unmodified strand, accompanied by a change in the hybridization of the thymine C-5 and C-6 carbons and a change in the local helix twist. The MAf is intercalated in the helix. There is no significant bend in the helix axis of either the MAf or XL. There are significant changes in the local helix dynamics upon photoadduct formation that may be recognized by cellular DNA repair enzyme systems. We hypothesize that the repair enzymes target lesions by detecting the conformational flexibility of the sugar-phosphate backbone induced by DNA-damaging agents.