Topoisomerase II Poisons: Converting Essential Enzymes into Molecular Scissors.
Topoisomerase II Poisons: Converting Essential Enzymes into Molecular Scissors.
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拓扑异构酶II毒素：将必需酶转化为分子剪刀。
DOI：
10.1021/acs.biochem.1c00240
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发表时间：
2021-06-01
期刊：
影响因子：
2.9
通讯作者：
Osheroff N
中科院分区：
文献类型：
--
作者：
Vann KR;Oviatt AA;Osheroff N
DNA的长度、紧密性和相互缠绕的性质，以及它在真核细胞中受控和受限的运动，产生了许多深刻影响遗传物质所有功能的拓扑问题。拓扑异构酶是调节双螺旋拓扑结构的必需酶，包括调节DNA的欠缠绕和过缠绕以及从基因组中去除缠结和结。II型拓扑异构酶通过在一个DNA片段中产生瞬时双链断裂并允许另一个片段通过DNA门来改变DNA拓扑结构。这些酶参与真核细胞中的许多关键核过程，如DNA复制、转录和重组，并且是正确的染色体结构和分离所必需的。然而，由于II型拓扑异构酶在遗传物质中产生双链断裂，因此它们也是具有使基因组片段化的能力的固有危险酶。由于这种二元性质，II型拓扑异构酶是许多广泛处方的抗癌药物的靶点。本文将描述真核生物II型拓扑异构酶的结构和催化机制，并将继续讨论拓扑异构酶II毒物的作用，这些毒物是稳定II型酶产生的DNA断裂并将这些必需酶转化为“分子剪刀”的化合物。拓扑异构酶II毒物代表广泛的结构类别，包括抗癌药物、膳食成分和环境化学品。
The extensive length, compaction, and interwound nature of DNA, together with its controlled and restricted movement in eukaryotic cells, create a number of topological issues that profoundly affect all of the functions of the genetic material. Topoisomerases are essential enzymes that modulate the topological structure of the double helix, including the regulation of DNA under- and overwinding and the removal of tangles and knots from the genome. Type II topoisomerases alter DNA topology by generating a transient double-stranded break in one DNA segment and allowing another segment to pass through the DNA gate. These enzymes are involved in a number of critical nuclear processes in eukaryotic cells, such as DNA replication, transcription and recombination, and are required for proper chromosome structure and segregation. However, because type II topoisomerases generate double-stranded breaks in the genetic material, they also are intrinsically dangerous enzymes that have the capacity to fragment the genome. As a result of this dualistic nature, type II topoisomerases are the targets for a number of widely prescribed anticancer drugs. This article will describe the structure and catalytic mechanism of eukaryotic type II topoisomerases and will go on to discuss the actions of topoisomerase II poisons, which are compounds that stabilize DNA breaks generated by the type II enzyme and convert these essential enzymes into “molecular scissors.” Topoisomerase II poisons represent a broad range of structural classes and include anticancer drugs, dietary components, and environmental chemicals.
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影响因子：
5.6
作者：
Austin CA;Lee KC;Swan RL;Khazeem MM;Manville CM;Cridland P;Treumann A;Porter A;Morris NJ;Cowell IG
通讯作者：
Cowell IG
DOI：
10.2174/1568011054222364
发表时间：
2005-07-01
期刊：
Current Medicinal Chemistry - Anti-Cancer Agents
影响因子：
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作者：
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通讯作者：
Osheroff, N.
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作者：
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影响因子：
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作者：
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通讯作者：
Osheroff, N
DOI：
10.1016/j.mrfmmm.2020.111711
发表时间：
2020-05-01
影响因子：
2.3
作者：
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通讯作者：
Chakraborty, Prasun