The role of ATP in the reactions of type II DNA topoisomerases

Bates, Andrew D.; Maxwell, Anthony

doi:10.1042/bst0380438

Cited by 21 publications

(17 citation statements)

References 22 publications

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“…However, in contrast to DNA supercoiling by gyrase, the amount of free energy required here is insignificant (<1%) compared with the total free energy available from ATP hydrolysis (16). Actually, all type-IIA consume ATP, regardless of the energetics of the topology interconversions (42,43). These premises have led to the proposal that the main and ancestral role of ATP is the coordination of the enzyme gates to prevent DNA double-strand breaks (41,44).…”

Section: Discussionmentioning

confidence: 99%

Topoisomerase II minimizes DNA entanglements by proofreading DNA topology after DNA strand passage

Martínez‐García

Fernández

Díaz-Ingelmo

et al. 2013

Nucleic Acids Research

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By transporting one DNA double helix (T-segment) through a double-strand break in another (G-segment), topoisomerase II reduces fractions of DNA catenanes, knots and supercoils to below equilibrium values. How DNA segments are selected to simplify the equilibrium DNA topology is enigmatic, and the biological relevance of this activity is unclear. Here we examined the transit of the T-segment across the three gates of topoisomerase II (entry N-gate, DNA-gate and exit C-gate). Our experimental results uncovered that DNA transport probability is determined not only during the capture of a T-segment at the N-gate. When a captured T-segment has crossed the DNA-gate, it can backtrack to the N-gate instead of exiting by the C-gate. When such backtracking is precluded by locking the N-gate or by removing the C-gate, topoisomerase II no longer simplifies equilibrium DNA topology. Therefore, we conclude that the C-gate enables a post-DNA passage proofreading mechanism, which challenges the release of passed T-segments to either complete or cancel DNA transport. This proofreading activity not only clarifies how type-IIA topoisomerases simplify the equilibrium topology of DNA in free solution, but it may explain also why these enzymes are able to solve the topological constraints of intracellular DNA without randomly entangling adjacent chromosomal regions.

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Section: Discussionmentioning

confidence: 99%

Topoisomerase II minimizes DNA entanglements by proofreading DNA topology after DNA strand passage

Martínez‐García

Fernández

Díaz-Ingelmo

et al. 2013

Nucleic Acids Research

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“…In the cases of gyrase (type IIA) and reverse gyrase, which introduce negative and positive supercoils to DNA, respectively, the requirement for the high-energy cofactor ATP is self-evident. The reason for the ATP-hydrolysis dependence of type II topoisomerases that relax (−) and (+) supercoils is less clear (Bates and Maxwell). ATP may play an essential regulatory role in coordinating the double-strand cleavage with DNA passage and avoiding hazardous double-strand breaks.…”

Section: Topoisomerization By Topib Topo Ia and Topo IImentioning

confidence: 99%

Topoisomerases and site-specific recombinases: similarities in structure and mechanism

Yang

2010

Critical Reviews in Biochemistry and Molecular Biology

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The processes of DNA topoisomerization and site-specific recombination are fundamentally similar: DNA cleavage by forming a phospho-protein covalent linkage, DNA topological rearrangement, and DNA ligation coupled with protein regeneration. Type IB DNA topoisomerases are structurally and mechanistically homologous to tyrosine recombinases. Both enzymes nick DNA double helices independent of metal ions, form 3´-phosphotyrosine intermediates, and rearrange the free 5´ ends relative to the uncut strands by swiveling. In contrast, serine recombinases generate 5´-phospho-serine intermediates. A 180° relative rotation of the two halves of a 100kDa terameric serine recombinase and DNA complex has been proposed as the mechanism of strand exchange. Here I propose an alternative mechanism. Interestingly, the catalytic domain of serine recombinases has structural similarity to the TOPRIM domain, conserved among all Type IA and Type II topoisomerases and responsible for metal binding and DNA cleavage. TOPRIM topoisomerases also cleave DNA to generate 5´-phosphate and 3´-OH groups. Based on the existing biochemical data and crystal structures of Topoisomerase II and serine recombinases bound to pre- and post-cleavage DNA, I suggest a strand passage mechanism for DNA recombination by serine recombinases. This mechanism is reminiscent of DNA topoisomerization and does not require subunit rotation.

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“…While type IIA topoisomerases are composed of two inter-connected rings, type IIB enzymes adopt the overall architecture of a single molecular clamp that contains the two first gates structurally related to the type IIA enzymes (N-ring) (Figure 1a and b). The current model of the DNA strand-passage reaction proposes that both enzyme subclasses bind two DNA segments and catalyse the ATP-dependent transport of one intact DNA double helix (‘T-segment’), through a gate DNA segment that contains the enzyme-mediated transient DNA gate (‘G-segment’) (1,6,7). To accomplish this task, topo IIA acts like two well-synchronized molecular clamps that alternatively capture and release DNA through three gates: the entrance ‘N-gate’, the ‘DNA gate’ and the exit or ‘C-gate’ (8) (Figure 1c).…”

Section: Introductionmentioning

confidence: 99%

Local sensing of global DNA topology: from crossover geometry to type II topoisomerase processivity

Timsit

2011

Nucleic Acids Research

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Type II topoisomerases are ubiquitous enzymes that control the topology and higher order structures of DNA. Type IIA enzymes have the remarkable property to sense locally the global DNA topology. Although many theoretical models have been proposed, the molecular mechanism of chiral discrimination is still unclear. While experimental studies have established that topoisomerases IIA discriminate topology on the basis of crossover geometry, a recent single-molecule experiment has shown that the enzyme has a different processivity on supercoiled DNA of opposite sign. Understanding how cross-over geometry influences enzyme processivity is, therefore, the key to elucidate the mechanism of chiral discrimination. Analysing this question from the DNA side reveals first, that the different stability of chiral DNA cross-overs provides a way to locally sense the global DNA topology. Second, it shows that these enzymes have evolved to recognize the G- and T-segments stably assembled into a right-handed cross-over. Third, it demonstrates how binding right-handed cross-overs across their large angle imposes a different topological link between the topoIIA rings and the plectonemes of opposite sign thus directly affecting the enzyme freedom of motion and processivity. In bridging geometry and kinetic data, this study brings a simple solution for type IIA topoisomerase chiral discrimination.

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The role of ATP in the reactions of type II DNA topoisomerases

Cited by 21 publications

References 22 publications

Topoisomerase II minimizes DNA entanglements by proofreading DNA topology after DNA strand passage

Topoisomerase II minimizes DNA entanglements by proofreading DNA topology after DNA strand passage

Topoisomerases and site-specific recombinases: similarities in structure and mechanism

Local sensing of global DNA topology: from crossover geometry to type II topoisomerase processivity

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