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Anticooperative Binding Governs the Mechanics of Ethidium-Complexed DNA
- Source :
- Biophysical Journal. 116:1394-1405
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- DNA intercalators bind nucleic acids by stacking between adjacent basepairs. This causes a considerable elongation of the DNA backbone as well as untwisting of the double helix. In the past few years, single-molecule mechanical experiments have become a common tool to characterize these deformations and to quantify important parameters of the intercalation process. Parameter extraction typically relies on the neighbor-exclusion model, in which a bound intercalator prevents intercalation into adjacent sites. Here, we challenge the neighbor-exclusion model by carefully quantifying and modeling the force-extension and twisting behavior of single ethidium-complexed DNA molecules. We show that only an anticooperative ethidium binding that allows for a disfavored but nonetheless possible intercalation into nearest-neighbor sites can consistently describe the mechanical behavior of intercalator-bound DNA. At high ethidium concentrations and elevated mechanical stress, this causes an almost complete occupation of nearest-neighbor sites and almost a doubling of the DNA contour length. We furthermore show that intercalation into nearest-neighbor sites needs to be considered when estimating intercalator parameters from zero-stress elongation and twisting data. We think that the proposed anticooperative binding mechanism may also be applicable to other intercalating molecules.
- Subjects :
- Models, Molecular
Intercalation (chemistry)
Biophysics
Stacking
Biophysical Phenomena
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Ethidium
Molecule
030304 developmental biology
0303 health sciences
Binding Sites
Chemistry
Articles
DNA
Intercalating Agents
Helix
Nucleic acid
Nucleic Acid Conformation
Thermodynamics
Contour length
Elongation
Hydrophobic and Hydrophilic Interactions
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 00063495
- Volume :
- 116
- Database :
- OpenAIRE
- Journal :
- Biophysical Journal
- Accession number :
- edsair.doi.dedup.....899f9015de070a0dce6df42eab25892e