Telling Your Right Hand from Your Left: The Effects of DNA Supercoil Handedness on the Actions of Type II Topoisomerases.

Telling Your Right Hand from Your Left: The Effects of DNA Supercoil Handedness on the Actions of Type II Topoisomerases.
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DOI:
10.3390/ijms241311199
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发表时间:
2023-07-07
影响因子:
5.6
通讯作者:
Osheroff, Neil
Osheroff, Neil
中科院分区:
生物学2区
文献类型:
--
作者:
Jian, Jeffrey Y. Y.;Osheroff, Neil

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II 型拓扑异构酶是调节所有生物体 DNA 超螺旋拓扑状态的必需酶。这些酶通过在过度缠绕或缠绕不足的 DNA 底物上进行双链传代反应来改变 DNA 拓扑结构。这种链传递反应会产生一种瞬时共价酶切割的 DNA 结构,称为切割复合物。尽管裂解复合物是必需的催化中间体,但它本质上对生物系统中的基因组稳定性也有危险。 II 型拓扑异构酶功能的潜在威胁也可能因超螺旋 DNA 底物的性质而异。在 DNA 复制和转录等重要过程中,与缠绕不足的 DNA 底物相比,缠绕过度的 DNA 底物上形成的裂解复合物本质上更加危险。因此,了解 DNA 拓扑结构对 II 型拓扑异构酶的细胞功能产生的深远影响非常重要。本综述将对人类和细菌 II 型拓扑异构酶如何识别和作用于各种拓扑状态的底物进行广泛的评估。
Type II topoisomerases are essential enzymes that modulate the topological state of DNA supercoiling in all living organisms. These enzymes alter DNA topology by performing double-stranded passage reactions on over- or underwound DNA substrates. This strand passage reaction generates a transient covalent enzyme–cleaved DNA structure known as the cleavage complex. Al-though the cleavage complex is a requisite catalytic intermediate, it is also intrinsically dangerous to genomic stability in biological systems. The potential threat of type II topoisomerase function can also vary based on the nature of the supercoiled DNA substrate. During essential processes such as DNA replication and transcription, cleavage complex formation can be inherently more dangerous on overwound versus underwound DNA substrates. As such, it is important to understand the profound effects that DNA topology can have on the cellular functions of type II topoisomerases. This review will provide a broad assessment of how human and bacterial type II topoisomerases recognize and act on their substrates of various topological states.
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