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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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Typical simulated conformation of knotted (top) and unknotted (bottom) 7-kb DNA molecules. Each of the shown conformations has a segment located inside the hairpin-like G segment (red). For both conformations the potential T segment and G segment, which could interact with the enzyme, are circled by the dashed line. It seems clear from the figure that the mutual path of the segments inside the circle cannot specify topology of the entire chains. Indeed, the topology of both conformations can be easily changed outside the dashed circles. The conformations were selected from the equilibrium ensemble generated by a Metropolis Monte Carlo procedure (5).
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Figure 3: Typical simulated conformation of knotted (top) and unknotted (bottom) 7-kb DNA molecules. Each of the shown conformations has a segment located inside the hairpin-like G segment (red). For both conformations the potential T segment and G segment, which could interact with the enzyme, are circled by the dashed line. It seems clear from the figure that the mutual path of the segments inside the circle cannot specify topology of the entire chains. Indeed, the topology of both conformations can be easily changed outside the dashed circles. The conformations were selected from the equilibrium ensemble generated by a Metropolis Monte Carlo procedure (5).

Mentions: In solution, large DNA molecules form very irregular random conformations. The average size of these conformations is around 500 nm for DNA molecules of 7–10 kb in length, so they are many times larger than the enzymes. These conformations continually change due to thermal motion, and there is no way for the enzymes determining topology of such DNA molecules to change it in a desired direction. This is illustrated by Figure 3, which shows typical simulated conformations DNA molecules with different topologies. It does not mean, however, that the enzymes cannot address the problem. They have to use the local statistical properties of the molecule random conformations that may be different for the molecules with different topology. Nearly all models suggested to explain the phenomenon tried to use these properties (4–7).Figure 3.


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

Vologodskii A - Nucleic Acids Res. (2009)

Typical simulated conformation of knotted (top) and unknotted (bottom) 7-kb DNA molecules. Each of the shown conformations has a segment located inside the hairpin-like G segment (red). For both conformations the potential T segment and G segment, which could interact with the enzyme, are circled by the dashed line. It seems clear from the figure that the mutual path of the segments inside the circle cannot specify topology of the entire chains. Indeed, the topology of both conformations can be easily changed outside the dashed circles. The conformations were selected from the equilibrium ensemble generated by a Metropolis Monte Carlo procedure (5).
© Copyright Policy - openaccess
Related In: Results  -  Collection

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

Figure 3: Typical simulated conformation of knotted (top) and unknotted (bottom) 7-kb DNA molecules. Each of the shown conformations has a segment located inside the hairpin-like G segment (red). For both conformations the potential T segment and G segment, which could interact with the enzyme, are circled by the dashed line. It seems clear from the figure that the mutual path of the segments inside the circle cannot specify topology of the entire chains. Indeed, the topology of both conformations can be easily changed outside the dashed circles. The conformations were selected from the equilibrium ensemble generated by a Metropolis Monte Carlo procedure (5).
Mentions: In solution, large DNA molecules form very irregular random conformations. The average size of these conformations is around 500 nm for DNA molecules of 7–10 kb in length, so they are many times larger than the enzymes. These conformations continually change due to thermal motion, and there is no way for the enzymes determining topology of such DNA molecules to change it in a desired direction. This is illustrated by Figure 3, which shows typical simulated conformations DNA molecules with different topologies. It does not mean, however, that the enzymes cannot address the problem. They have to use the local statistical properties of the molecule random conformations that may be different for the molecules with different topology. Nearly all models suggested to explain the phenomenon tried to use these properties (4–7).Figure 3.

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