How do type II topoisomerases use ATP hydrolysis to simplify DNA topology beyond equilibrium? Investigating the relaxation reaction of nonsupercoiling type II topoisomerases.
How do type II topoisomerases use ATP hydrolysis to simplify DNA topology beyond equilibrium? Investigating the relaxation reaction of nonsupercoiling type II topoisomerases.
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DOI：
10.1016/j.jmb.2008.11.056
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发表时间：
2009-02-06
影响因子：
5.6
通讯作者：
Maxwell, Anthony
中科院分区：
文献类型：
--
作者：
Stuchinskaya, Tanya;Mitchenall, Lesley A.;Schoeffler, Allyn J.;Corbett, Kevin D.;Berger, James M.;Bates, Andrew D.;Maxwell, Anthony
DNA拓扑异构酶控制所有细胞中DNA的拓扑结构（例如超螺旋的水平）。IIA型拓扑异构酶是ATP依赖性酶，已显示其将其DNA底物的拓扑结构简化至超过平衡时预期的水平（即比ATP非依赖性酶（如I型拓扑异构酶）的松弛产物更松弛，或低于平衡水平的连锁）。这种效应的机制目前尚不清楚，尽管已经提出了几种模型。我们分析了II型拓扑异构酶的DNA弛豫反应以进一步探索这一现象。我们发现，所有的IIA型拓扑异构酶测试表现出类似程度的效果，它是不依赖于C-末端结构域的酶。如最近报道的，IIB型拓扑异构酶，拓扑VI（其仅与IIA型酶有远亲关系）不表现出拓扑简化。我们发现，拓扑结构的简化是不显着依赖于环的大小在2-9 kbp的范围内，并没有改变通过改变ATP：ADP比例减少ATP水解的自由能。对一个模型（DNA追踪，即蛋白质钳沿着DNA滑动以捕获超螺旋）的直接测试表明，这不太可能是对该效应的解释。我们的结论是，几何选择的DNA片段的酶可能是一个主要来源的效果，但它是可能的，其他因素的贡献。我们还推测拓扑简化是否可能只是一个进化的遗物，没有适应意义。
DNA topoisomerases control the topology of DNA (e.g. the level of supercoiling) in all cells. Type IIA topoisomerases are ATP-dependent enzymes that have been shown to simplify the topology of their DNA substrates to a level beyond that expected at equilibrium (i.e. more relaxed than the product of relaxation by ATP-independent enzymes, such as type I topoisomerases, or a lower than equilibrium level of catenation). The mechanism of this effect is currently unknown, although several models have been suggested. We have analysed the DNA relaxation reactions of type II topoisomerases to further explore this phenomenon. We find that all type IIA topoisomerases tested exhibit the effect to a similar degree and that it is not dependent on the C-terminal domains of the enzymes. As recently reported, the type IIB topoisomerase, topo VI (which is only distantly related to the type IIA enzymes), does not exhibit topology simplification. We find that topology simplification is not significantly dependent on circle size in the range ~2–9 kbp, and is not altered by reducing the free energy available from ATP hydrolysis by varying the ATP:ADP ratio. A direct test of one model (DNA tracking, i.e. sliding of a protein clamp along DNA to trap supercoils) suggests that this is unlikely to be the explanation for the effect. We conclude that geometric selection of DNA segments by the enzymes is likely to be a primary source of the effect but that it is possible that other factors contribute. We also speculate whether topology simplification might simply be an evolutionary relic, with no adaptive significance.
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影响因子：
14.9
作者：
Burnier Y;Dorier J;Stasiak A
通讯作者：
Stasiak A
影响因子：
5.3
作者：
GANGLOFF, S;MCDONALD, JP;ROTHSTEIN, R
通讯作者：
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影响因子：
2.9
作者：
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Osheroff, Neil
DOI：
10.1073/pnas.93.25.14416
发表时间：
1996-12-10
影响因子：
11.1
作者：
Kampranis, SC;Maxwell, A
通讯作者：
Maxwell, A
影响因子：
2.9
作者：
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通讯作者：
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