拓扑异构酶 II 对 DNA 断裂位点的选择源于酶诱导的 DNA 柔韧性。
Selection of DNA Cleavage Sites by Topoisomerase II Results from Enzyme-Induced Flexibility of DNA.
机构信息
Advanced Photonics Research Institute, Gwangju Institute of Science and Technology, Gwangju 61005, South Korea.
Department of Physics and Astronomy, National Center for Creative Research Initiatives, Seoul National University, Seoul 08826, South Korea.
出版信息
Cell Chem Biol. 2019 Apr 18;26(4):502-511.e3. doi: 10.1016/j.chembiol.2018.12.003. Epub 2019 Jan 31.
Abstract
Topoisomerase II cleaves DNA at preferred sequences with different efficiencies; however, the mechanism of cleavage site selection is not known. Here we used single-molecule fluorescence assays that monitor several critical steps of DNA-topoisomerase II interactions, including binding/dissociation, bending/straightening, and cleavage/religation, and reveal that the cleavage site is selected mainly during the bending step. Furthermore, despite the sensitivity of the bending rate to the DNA sequence, it is not an intrinsic property of the DNA itself. Rather, it is determined by protein-DNA interactions.
摘要
拓扑异构酶 II 在不同效率下在优选序列处切割 DNA；然而，切割位点选择的机制尚不清楚。在这里，我们使用单分子荧光分析方法来监测 DNA-拓扑异构酶 II 相互作用的几个关键步骤，包括结合/解离、弯曲/变直和切割/连接，并揭示了切割位点主要在弯曲步骤中被选择。此外，尽管弯曲速率对 DNA 序列很敏感，但它不是 DNA 本身的固有特性。相反，它是由蛋白-DNA 相互作用决定的。
相似文献
1
Selection of DNA Cleavage Sites by Topoisomerase II Results from Enzyme-Induced Flexibility of DNA.拓扑异构酶 II 对 DNA 断裂位点的选择源于酶诱导的 DNA 柔韧性。
Cell Chem Biol. 2019 Apr 18;26(4):502-511.e3. doi: 10.1016/j.chembiol.2018.12.003. Epub 2019 Jan 31.
2
DNA topoisomerases as targets for the anticancer drug TAS-103: primary cellular target and DNA cleavage enhancement.DNA拓扑异构酶作为抗癌药物TAS-103的靶点：主要细胞靶点及DNA切割增强作用
Biochemistry. 1999 Nov 23;38(47):15573-9. doi: 10.1021/bi991791o.
3
Mode of action of topoisomerase II-targeting agents at a specific DNA sequence. Uncoupling the DNA binding, cleavage and religation events.靶向拓扑异构酶II的药物在特定DNA序列处的作用模式。使DNA结合、切割和重新连接事件解偶联。
J Mol Biol. 1992 Dec 5;228(3):778-86. doi: 10.1016/0022-2836(92)90863-f.
4
DNA cleavage and opening reactions of human topoisomerase IIα are regulated via Mg2+-mediated dynamic bending of gate-DNA.人类拓扑异构酶 IIα 的 DNA 切割和打开反应通过 Mg2+ 介导的门控 DNA 的动态弯曲进行调节。
Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):2925-30. doi: 10.1073/pnas.1115704109. Epub 2012 Feb 9.
5
In vitro evolution of preferred topoisomerase II DNA cleavage sites.拓扑异构酶II偏好性DNA切割位点的体外进化
J Biol Chem. 1999 Feb 19;274(8):5227-35. doi: 10.1074/jbc.274.8.5227.
6
DNA topoisomerases as targets for the anticancer drug TAS-103: DNA interactions and topoisomerase catalytic inhibition.作为抗癌药物TAS-103作用靶点的DNA拓扑异构酶：DNA相互作用及拓扑异构酶催化抑制作用
Biochemistry. 1999 Nov 23;38(47):15580-6. doi: 10.1021/bi991792g.
7
Interdomain communication in DNA topoisomerase II. DNA binding and enzyme activation.DNA拓扑异构酶II中的结构域间通讯。DNA结合与酶激活。
J Biol Chem. 2006 Aug 18;281(33):23395-404. doi: 10.1074/jbc.M604119200. Epub 2006 Jun 16.
8
The probabilities of supercoil removal and decatenation by yeast DNA topoisomerase II.酵母DNA拓扑异构酶II去除超螺旋和解开连环的概率。
Genes Cells. 1996 Jan;1(1):17-27. doi: 10.1046/j.1365-2443.1996.01001.x.
9
Topoisomerase II binds to ellipticine in the absence or presence of DNA. Characterization of enzyme-drug interactions by fluorescence spectroscopy.在有无DNA的情况下，拓扑异构酶II均可与椭圆玫瑰树碱结合。通过荧光光谱法表征酶-药物相互作用。
J Biol Chem. 1995 Jun 23;270(25):14998-5004. doi: 10.1074/jbc.270.25.14998.
10
Double-stranded DNA cleavage/religation reaction of eukaryotic topoisomerase II: evidence for a nicked DNA intermediate.真核生物拓扑异构酶II的双链DNA切割/连接反应：存在带切口DNA中间体的证据
Biochemistry. 1989 Jul 25;28(15):6229-36. doi: 10.1021/bi00441a014.
引用本文的文献
1
Bacterial type II topoisomerases cleave DNA in a species-specific manner.细菌II型拓扑异构酶以物种特异性方式切割DNA。
bioRxiv. 2025 Jul 28:2025.07.28.667256. doi: 10.1101/2025.07.28.667256.
2
Fuzzy protein-DNA interactions and beyond: A common theme in transcription?模糊的蛋白质-DNA 相互作用及其他：转录中的一个共同主题？
Curr Opin Struct Biol. 2024 Dec;89:102941. doi: 10.1016/j.sbi.2024.102941. Epub 2024 Oct 17.
3
Target-Mediated Fluoroquinolone Resistance in : Actions of Ciprofloxacin against Gyrase and Topoisomerase IV.氟喹诺酮类药物的靶向耐药性：环丙沙星对拓扑异构酶 II 和拓扑异构酶 IV 的作用。
ACS Infect Dis. 2024 Apr 12;10(4):1351-1360. doi: 10.1021/acsinfecdis.4c00041. Epub 2024 Mar 4.
4
Gyrase and Topoisomerase IV: Recycling Old Targets for New Antibacterials to Combat Fluoroquinolone Resistance.回旋酶和拓扑异构酶 IV：回收旧靶点用于新型抗菌药物以对抗氟喹诺酮耐药性。
ACS Infect Dis. 2024 Apr 12;10(4):1097-1115. doi: 10.1021/acsinfecdis.4c00128. Epub 2024 Apr 2.
5
Telling Your Right Hand from Your Left: The Effects of DNA Supercoil Handedness on the Actions of Type II Topoisomerases.辨别左右手：DNA 超螺旋手性对 II 型拓扑异构酶作用的影响。
Int J Mol Sci. 2023 Jul 7;24(13):11199. doi: 10.3390/ijms241311199.
6
Extensive Bioinformatics Analyses Reveal a Phylogenetically Conserved Winged Helix (WH) Domain (Zτ) of Topoisomerase IIα, Elucidating Its Very High Affinity for Left-Handed Z-DNA and Suggesting Novel Putative Functions.广泛的生物信息学分析揭示拓扑异构酶 IIα 具有系统进化保守的翼状螺旋（WH）结构域（Zτ），阐明其对左手 Z-DNA 的极高亲和力，并提出新的潜在功能。
Int J Mol Sci. 2023 Jun 27;24(13):10740. doi: 10.3390/ijms241310740.
7
Mg-dependent conformational rearrangements of CRISPR-Cas12a R-loop complex are mandatory for complete double-stranded DNA cleavage.Mg 依赖性构象重排是 CRISPR-Cas12a R 环复合物完成双链 DNA 切割所必需的。
Proc Natl Acad Sci U S A. 2021 Dec 7;118(49). doi: 10.1073/pnas.2113747118.
8
Spo11 generates gaps through concerted cuts at sites of topological stress.Spo11通过在拓扑应力位点协同切割产生缺口。
Nature. 2021 Jun;594(7864):577-582. doi: 10.1038/s41586-021-03632-x. Epub 2021 Jun 9.
9
Structural basis for allosteric regulation of Human Topoisomerase IIα.别构调节人拓扑异构酶 IIα 的结构基础。
Nat Commun. 2021 May 20;12(1):2962. doi: 10.1038/s41467-021-23136-6.
10
Topoisomerase II Poisons: Converting Essential Enzymes into Molecular Scissors.拓扑异构酶 II 抑制剂：将必需酶转化为分子剪刀。
Biochemistry. 2021 Jun 1;60(21):1630-1641. doi: 10.1021/acs.biochem.1c00240. Epub 2021 May 19.
本文引用的文献
1
Roles of eukaryotic topoisomerases in transcription, replication and genomic stability.真核生物拓扑异构酶在转录、复制和基因组稳定性中的作用。
Nat Rev Mol Cell Biol. 2016 Nov;17(11):703-721. doi: 10.1038/nrm.2016.111. Epub 2016 Sep 21.
2
Probing the elastic limit of DNA bending.探究DNA弯曲的弹性极限。
Nucleic Acids Res. 2014;42(16):10786-94. doi: 10.1093/nar/gku735. Epub 2014 Aug 13.
3
Topoisomerase II and leukemia.拓扑异构酶 II 与白血病。
Ann N Y Acad Sci. 2014 Mar;1310(1):98-110. doi: 10.1111/nyas.12358. Epub 2014 Feb 3.
4
DNA sequence-dependent mechanics and protein-assisted bending in repressor-mediated loop formation.阻遏蛋白介导的环形成中 DNA 序列依赖的力学性质和蛋白辅助的弯曲。
Phys Biol. 2013 Dec;10(6):066005. doi: 10.1088/1478-3975/10/6/066005. Epub 2013 Nov 15.
5
Measuring shape-dependent looping probability of DNA.测量 DNA 形状依赖性环化概率。
Biophys J. 2013 May 7;104(9):2068-76. doi: 10.1016/j.bpj.2013.03.029.
6
The role of DNA bending in type IIA topoisomerase function.DNA 弯曲在 IIA 拓扑异构酶功能中的作用。
Nucleic Acids Res. 2013 May 1;41(10):5444-56. doi: 10.1093/nar/gkt238. Epub 2013 Apr 10.
7
Autofocusing system based on optical astigmatism analysis of single-molecule images.基于单分子图像光学像散分析的自动聚焦系统。
Opt Express. 2012 Dec 31;20(28):29353-60. doi: 10.1364/OE.20.029353.
8
Extreme bendability of DNA less than 100 base pairs long revealed by single-molecule cyclization.单分子环化实验揭示了长度小于 100 个碱基对的 DNA 的极端柔韧性。
Science. 2012 Aug 31;337(6098):1097-101. doi: 10.1126/science.1224139.
9
The structure of DNA-bound human topoisomerase II alpha: conformational mechanisms for coordinating inter-subunit interactions with DNA cleavage.DNA 结合态人拓扑异构酶 IIα的结构：协调亚基间相互作用与 DNA 切割的构象机制。
J Mol Biol. 2012 Dec 7;424(3-4):109-24. doi: 10.1016/j.jmb.2012.07.014. Epub 2012 Jul 25.
10
DNA cleavage and opening reactions of human topoisomerase IIα are regulated via Mg2+-mediated dynamic bending of gate-DNA.人类拓扑异构酶 IIα 的 DNA 切割和打开反应通过 Mg2+ 介导的门控 DNA 的动态弯曲进行调节。
Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):2925-30. doi: 10.1073/pnas.1115704109. Epub 2012 Feb 9.
Zotero 插件