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Theoretical models of DNA topology simplification by type IIA DNA topoisomerases.

Vologodskii A - Nucleic Acids Res. (2009)

Bottom Line: Though this property of the enzymes made clear biological sense, it was not clear how small enzymes could selectively change the topology of very large DNA molecules, since topology is a global property and cannot be determined by a local DNA-protein interaction.A few models, suggested to explain the phenomenon, are analyzed in this review.We also consider experimental data that both support and contravene these models.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, New York University, New York, NY 10003, USA. alex.vologodskii@nyu.edu

ABSTRACT
It was discovered 12 years ago that type IIA topoisomerases can simplify DNA topology--the steady-state fractions of knots and links created by the enzymes are many times lower than the corresponding equilibrium fractions. Though this property of the enzymes made clear biological sense, it was not clear how small enzymes could selectively change the topology of very large DNA molecules, since topology is a global property and cannot be determined by a local DNA-protein interaction. A few models, suggested to explain the phenomenon, are analyzed in this review. We also consider experimental data that both support and contravene these models.

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Related in: MedlinePlus

The model of type IIA topoisomerase action. The enzyme (red) bends the G segment of DNA into a hairpin-like conformation. The entrance gate for the T segment of DNA is inside the hairpin. Thus, the T segment can pass through the G segment only from inside to outside the hairpin. Although it is not clear that the suggested mechanism has to provide simplification of DNA topology, the computational analysis shows that it really does (5).
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Figure 4: The model of type IIA topoisomerase action. The enzyme (red) bends the G segment of DNA into a hairpin-like conformation. The entrance gate for the T segment of DNA is inside the hairpin. Thus, the T segment can pass through the G segment only from inside to outside the hairpin. Although it is not clear that the suggested mechanism has to provide simplification of DNA topology, the computational analysis shows that it really does (5).

Mentions: In an attempt to explain the phenomena, we suggested that the enzymes create a sharp bend in the G segment (5). If the enzymes create such a bend, they have to have a specific orientation relative to the bend. Thus, the complex with the bent G segment can provide a unidirectional passage of the T segment from inside to outside the hairpin formed by the G segment (Figure 4). Indeed, it had been known that the enzymes catalyze the passage of a T segment in one direction relative to themselves (13). A unidirectional transport requires energy that is supplied by ATP hydrolysis coupled with the strand-passing. Thus, the model suggests a reason for this unidirectional strand-passing which was difficult to understand. The directionality of strand passage is only local, since the hairpin can have any orientation relative to the DNA chain. Surprisingly though, the quantitative analysis of the model showed that it predicts a large decrease of the steady state fractions of knots and catenanes relative to the equilibrium fractions (5).Figure 4.


Theoretical models of DNA topology simplification by type IIA DNA topoisomerases.

Vologodskii A - Nucleic Acids Res. (2009)

The model of type IIA topoisomerase action. The enzyme (red) bends the G segment of DNA into a hairpin-like conformation. The entrance gate for the T segment of DNA is inside the hairpin. Thus, the T segment can pass through the G segment only from inside to outside the hairpin. Although it is not clear that the suggested mechanism has to provide simplification of DNA topology, the computational analysis shows that it really does (5).
© Copyright Policy - openaccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2691845&req=5

Figure 4: The model of type IIA topoisomerase action. The enzyme (red) bends the G segment of DNA into a hairpin-like conformation. The entrance gate for the T segment of DNA is inside the hairpin. Thus, the T segment can pass through the G segment only from inside to outside the hairpin. Although it is not clear that the suggested mechanism has to provide simplification of DNA topology, the computational analysis shows that it really does (5).
Mentions: In an attempt to explain the phenomena, we suggested that the enzymes create a sharp bend in the G segment (5). If the enzymes create such a bend, they have to have a specific orientation relative to the bend. Thus, the complex with the bent G segment can provide a unidirectional passage of the T segment from inside to outside the hairpin formed by the G segment (Figure 4). Indeed, it had been known that the enzymes catalyze the passage of a T segment in one direction relative to themselves (13). A unidirectional transport requires energy that is supplied by ATP hydrolysis coupled with the strand-passing. Thus, the model suggests a reason for this unidirectional strand-passing which was difficult to understand. The directionality of strand passage is only local, since the hairpin can have any orientation relative to the DNA chain. Surprisingly though, the quantitative analysis of the model showed that it predicts a large decrease of the steady state fractions of knots and catenanes relative to the equilibrium fractions (5).Figure 4.

Bottom Line: Though this property of the enzymes made clear biological sense, it was not clear how small enzymes could selectively change the topology of very large DNA molecules, since topology is a global property and cannot be determined by a local DNA-protein interaction.A few models, suggested to explain the phenomenon, are analyzed in this review.We also consider experimental data that both support and contravene these models.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, New York University, New York, NY 10003, USA. alex.vologodskii@nyu.edu

ABSTRACT
It was discovered 12 years ago that type IIA topoisomerases can simplify DNA topology--the steady-state fractions of knots and links created by the enzymes are many times lower than the corresponding equilibrium fractions. Though this property of the enzymes made clear biological sense, it was not clear how small enzymes could selectively change the topology of very large DNA molecules, since topology is a global property and cannot be determined by a local DNA-protein interaction. A few models, suggested to explain the phenomenon, are analyzed in this review. We also consider experimental data that both support and contravene these models.

Show MeSH
Related in: MedlinePlus