The crystal structures of psoralen cross-linked DNAs: Drug-dependent formation of Holliday junctions
The crystal structures of psoralen cross-linked DNAs: Drug-dependent formation of Holliday junctions
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DOI：
10.1006/jmbi.2001.4567
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发表时间：
2001-04-20
影响因子：
5.6
通讯作者：
Ho, PS
中科院分区：
文献类型：
--
作者：
Eichman, BF;Mooers, BHM;Ho, PS
给出了两条 DNA 序列的单晶结构，其中胸腺嘧啶碱基通过 4'-羟甲基-4,5',8-三甲基补骨脂素 (HMT) 在互补链上共价交联。 d(CCGCTAGCGG) 的 HMT 加合物形成补骨脂素诱导的霍利迪连接体，首次显示了这一类重要化疗药物对重组中间体结构的影响。相反，HMT-d(CCGGTACCGG) 形成序列依赖性连接。在这两种结构中，DNA 双链体在与药物六元吡喃酮环相连的胸腺嘧啶碱基处高度扭曲。补骨脂素交联定义了药物诱导连接的分子内相互作用，而序列依赖性结构几乎与单独的 d(CCGGTACCGG) 的天然霍利迪连接相同。这两种结构对比了药物和序列依赖性相互作用对霍利迪连接体结构的影响，表明补骨脂素在哺乳动物 DNA 中补骨脂素损伤修复机制中的作用。 (C) 2001 年学术出版社。
The single-crystal structures are presented for two DNA sequences with the thymine bases covalently cross-linked across the complementary strands by 4 ' -hydroxymethyl-4,5 ' ,8-trimethylpsoralen (HMT). The HMT-adduct of d(CCGCTAGCGG) forms a psoralen-induced Holliday junction, showing for the first time the effect of this important class of chemotheraputics on the structure of the recombination intermediate. In contrast, HMT-d(CCGGTACCGG) forms a sequence-dependent junction. Ln both structures, the DNA duplex is highly distorted at the thymine base linked to the six-member pyrone ring of the drug. The psoralen cross-link defines the intramolecular interactions of the drug-induced junction, while the sequence-dependent structure is nearly identical to the native Holliday junction of d(CCGGTACCGG) alone. The two structures contrast the effects of drug- and sequence-dependent interactions on the structure of a Holliday junction, suggesting a role for psoralen in the mechanism to initiate repair of psoralen-lesions in mammalian DNA. (C) 2001 Academic Press.