Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg, CNRS UMR 7104, Inserm U 1258, 67400 Illkirch, France.
Hôpitaux Universitaires de Strasbourg, 67098 Strasbourg, France.
Int J Mol Sci. 2023 Feb 16;24(4):3986. doi: 10.3390/ijms24043986.
DNA topoisomerases have an essential role in resolving topological problems that arise due to the double-helical structure of DNA. They can recognise DNA topology and catalyse diverse topological reactions by cutting and re-joining DNA ends. Type IA and IIA topoisomerases, which work by strand passage mechanisms, share catalytic domains for DNA binding and cleavage. Structural information has accumulated over the past decades, shedding light on the mechanisms of DNA cleavage and re-ligation. However, the structural rearrangements required for DNA-gate opening and strand transfer remain elusive, in particular for the type IA topoisomerases. In this review, we compare the structural similarities between the type IIA and type IA topoisomerases. The conformational changes that lead to the opening of the DNA-gate and strand passage, as well as allosteric regulation, are discussed, with a focus on the remaining questions about the mechanism of type IA topoisomerases.
DNA 拓扑异构酶在解决由于 DNA 双螺旋结构而产生的拓扑问题方面发挥着重要作用。它们可以识别 DNA 拓扑结构，并通过切割和重新连接 DNA 末端来催化多种拓扑反应。通过链穿越机制发挥作用的 I 型和 IIA 拓扑异构酶共享用于 DNA 结合和切割的催化结构域。过去几十年积累的结构信息阐明了 DNA 切割和重新连接的机制。然而，DNA 门打开和链转移所需的结构重排仍然难以捉摸，特别是对于 I 型拓扑异构酶。在这篇综述中，我们比较了 IIA 型和 I 型拓扑异构酶之间的结构相似性。讨论了导致 DNA 门打开和链穿越的构象变化以及别构调节，重点讨论了关于 I 型拓扑异构酶机制的剩余问题。
