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DNA-Topology Simplification by Topoisomerases
- Source :
- Molecules, Vol 26, Iss 3375, p 3375 (2021), Molecules
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- The topological properties of DNA molecules, supercoiling, knotting, and catenation, are intimately connected with essential biological processes, such as gene expression, replication, recombination, and chromosome segregation. Non-trivial DNA topologies present challenges to the molecular machines that process and maintain genomic information, for example, by creating unwanted DNA entanglements. At the same time, topological distortion can facilitate DNA-sequence recognition through localized duplex unwinding and longer-range loop-mediated interactions between the DNA sequences. Topoisomerases are a special class of essential enzymes that homeostatically manage DNA topology through the passage of DNA strands. The activities of these enzymes are generally investigated using circular DNA as a model system, in which case it is possible to directly assay the formation and relaxation of DNA supercoils and the formation/resolution of knots and catenanes. Some topoisomerases use ATP as an energy cofactor, whereas others act in an ATP-independent manner. The free energy of ATP hydrolysis can be used to drive negative and positive supercoiling or to specifically relax DNA topologies to levels below those that are expected at thermodynamic equilibrium. The latter activity, which is known as topology simplification, is thus far exclusively associated with type-II topoisomerases and it can be understood through insight into the detailed non-equilibrium behavior of type-II enzymes. We use a non-equilibrium topological-network approach, which stands in contrast to the equilibrium models that are conventionally used in the DNA-topology field, to gain insights into the rates that govern individual transitions between topological states. We anticipate that our quantitative approach will stimulate experimental work and the theoretical/computational modeling of topoisomerases and similar enzyme systems.
- Subjects :
- Models, Molecular
Protein Conformation
non-equilibrium biophysics
Pharmaceutical Science
Organic chemistry
Review
Topology
DNA sequencing
Analytical Chemistry
03 medical and health sciences
chemistry.chemical_compound
Catenation
0302 clinical medicine
Adenosine Triphosphate
QD241-441
Drug Discovery
Site-specific recombination
Physical and Theoretical Chemistry
master equations
Topology (chemistry)
030304 developmental biology
0303 health sciences
biology
Chemistry
type-II topoisomerases
Topoisomerase
Hydrolysis
site-specific recombination
DNA
Molecular machine
DNA topology
Chemistry (miscellaneous)
biology.protein
Molecular Medicine
DNA supercoil
Nucleic Acid Conformation
030217 neurology & neurosurgery
DNA Topoisomerases
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Volume :
- 26
- Issue :
- 3375
- Database :
- OpenAIRE
- Journal :
- Molecules
- Accession number :
- edsair.doi.dedup.....c7ae999418e270fc791b8a994f943539