Interaction of human nuclear topoisomerase I with guanosine quartet-forming and guanosine-rich single-stranded DNA and RNA oligonucleotides
Interaction of human nuclear topoisomerase I with guanosine quartet-forming and guanosine-rich single-stranded DNA and RNA oligonucleotides
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DOI：
10.1074/jbc.m106372200
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发表时间：
2002-03-15
影响因子：
4.8
通讯作者：
Pommier, Y
中科院分区：
文献类型：
--
作者：
Marchand, C;Pourquier, P;Pommier, Y
人类核 DNA 拓扑异构酶 I (top1) 在 DNA 复制、转录和染色体浓缩中发挥着至关重要的作用。在这项研究中，我们证明分子内和分子间鸟苷四联体（G-四联体）可以在高亲和力位点抑制 top1 介导的 DNA 切割。 Top1 介导的 DNA 裂解也受到含有富含 G 序列 (G(2)T(2)G(5)TG(2)TG(3)) 的 16 聚体单链寡脱氧核苷酸 (ODN) 及其 RNA 等效物的抑制，两者均不形成 G 四联体结构。比较各种单链 ODN 抑制 top1 介导的 DNA 切割的能力表明，含有胸腺嘧啶间隔的 2 或 3 个连续鸟嘌呤重复序列的富含 G 的序列特异性抑制 top1。我们还发现单链和 G 四联体形成的 ODN 都与 top1 结合，而不被酶切割。这些结果表明，DNA 或 RNA 富含 G 的单链和 G 四联体形成寡核苷酸可以与 top1 结合并防止双链 DNA 的切割。
Human nuclear DNA topoisomerase I (top1) plays a crucial role in DNA replication, transcription, and chromosome condensation. In this study, we show that intra- and intermolecular guanosine quartets (G-quartets) can inhibit top1-mediated DNA cleavage at a high affinity site. Top1-mediated DNA cleavage was also inhibited by a 16-mer single-stranded oligodeoxynucleotide (ODN) containing a G-rich sequence (G(2)T(2)G(5)TG(2)TG(3)) and by its RNA equivalent, neither of which form G-quartet structures. A comparison of various single-stranded ODN for their ability to inhibit top1-mediated DNA cleavage indicated that G-rich sequences containing repeats of 2 or 3 consecutive guanines interspaced with thymines specifically inhibited top1. We also found that both single-stranded and G-quartet-forming ODNs bind to top1 without being cleaved by the enzyme. These results demonstrate that either DNA or RNA G-rich single-stranded and G-quartet-forming oligonucleotides can bind to top1 and prevent cleavage of duplex DNA.