The ancestral role of ATP hydrolysis in type II topoisomerases: prevention of DNA double-strand breaks.
The ancestral role of ATP hydrolysis in type II topoisomerases: prevention of DNA double-strand breaks.
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DOI：
10.1093/nar/gkr258
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发表时间：
2011-08
影响因子：
14.9
通讯作者：
Maxwell A
中科院分区：
文献类型：
--
作者：
Bates AD;Berger JM;Maxwell A
II型DNA拓扑异构酶（topos）通过使一个双链DNA片段通过另一个双链DNA片段来催化DNA拓扑结构的变化。这种反应对于复制和转录等过程是必不可少的，但也带来了永久性双链断裂（DSB）形成的固有危险。所有II型拓扑结构在它们的反应过程中水解ATP;然而，只有DNA促旋酶能够利用水解的自由能来驱动DNA超螺旋，这是一个能量上不利的过程。一个长期存在的难题是理解为什么大多数II型酶消耗ATP来支持不需要净能量输入的反应。虽然某些II型拓扑被称为“简化”的DNA拓扑异构体的分布低于热力学平衡水平，这个过程所需的能量是非常低的，这表明这种行为是不是ATP水解的主要原因。相反，我们建议，ATP水解的能量是需要控制蛋白质-蛋白质界面的分离，并防止意外形成潜在的致突变性或细胞毒性DSB。这种解释与催化生物大分子构象重排的各种分子机器的作用相似。
Type II DNA topoisomerases (topos) catalyse changes in DNA topology by passing one double-stranded DNA segment through another. This reaction is essential to processes such as replication and transcription, but carries with it the inherent danger of permanent double-strand break (DSB) formation. All type II topos hydrolyse ATP during their reactions; however, only DNA gyrase is able to harness the free energy of hydrolysis to drive DNA supercoiling, an energetically unfavourable process. A long-standing puzzle has been to understand why the majority of type II enzymes consume ATP to support reactions that do not require a net energy input. While certain type II topos are known to ‘simplify’ distributions of DNA topoisomers below thermodynamic equilibrium levels, the energy required for this process is very low, suggesting that this behaviour is not the principal reason for ATP hydrolysis. Instead, we propose that the energy of ATP hydrolysis is needed to control the separation of protein–protein interfaces and prevent the accidental formation of potentially mutagenic or cytotoxic DSBs. This interpretation has parallels with the actions of a variety of molecular machines that catalyse the conformational rearrangement of biological macromolecules.
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