Interaction of human DNA topoisomerase I with G-quartet structures

Interaction of human DNA topoisomerase I with G-quartet structures
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DOI:
10.1093/nar/28.24.4832
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发表时间:
2000-12-15
影响因子:
14.9
通讯作者:
Hélène, C
Hélène, C
中科院分区:
生物学2区
文献类型:
--
作者:
Arimondo, PB;Riou, JF;Hélène, C

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拓扑异构酶是一种普遍存在的重要酶,参与DNA的复制和转录等代谢过程。我们发现,拓扑异构酶I(Topo I)在G-四联体形成中起着意想不到的“分子媒人”作用,G-四链体是由四个鸟嘌呤(“G-四联体”)的正方形平面通过形成Hoogsteen氢键相互作用而保持在一起的多链结构。拓扑异构酶Ⅰ与含有至少5个鸟嘌呤的单链DNA形成四链DNA分子间结构,证明了这些复合物是由鸟嘌呤四联体介导的平行G-四联体结构。此外,拓扑异构酶Ⅰ与预先形成的平行和反平行G4-DNA特异性结合。
Because of their role in the control of the topological state of DNA, topoisomerases are ubiquitous and vital enzymes, which participate in nearly all events related to DNA metabolism including replication and transcription, We show here that human topoisomerase I (Topo I) plays an unexpected role of 'molecular matchmaker' for G-quartet formation, G-quadruplexes are multi-stranded structures held together by square planes of four guanines ('G-quartets') interacting by forming Hoogsteen hydrogen bonds. Topo I is able to promote the formation of four-stranded intermolecular DNA structures when added to single-stranded DNA containing a stretch of at least five guanines, We provide evidence that these complexes are parallel G-quartet structures, mediated by tetrads of hydrogen-bonded guanine, In addition, Topo I binds specifically to pre-formed parallel and anti-parallel G4-DNA.