A chiral theory of DNA supercoiling

Lead Research Organisation: University College London
Department Name: Civil Environmental and Geomatic Eng

Abstract

We propose to bring together three threads of recent progress to develop anew chiral theory of DNA supercoiling. The three threads are i) theelectrostatic theory of interacting helical charge distributions, ii) themechanical theory of elastic braids, and iii) a new efficient approach toderive equilibrium equations for geometric variational problems. The newtheory will for the first time introduce explicitly chiral interactions intothe description of supercoiling, and will uncover the effects driven by theseinteractions. Specifically, we will build a theory to describe foursupercoiling situations: (i) spontaneous formation of free-ended braids,(ii) conformations of braided DNA in single-molecule manipulation experiments,and formation of writhes in (iii) torsionally stressed and (iv) initiallyrelaxed looped DNA, triggered by changing environment.In recent years systematic experimental studies of the torque response ofplectonemically supercoiled and braided DNA have been performed, while moreare anticipated. These require a quantitative theory that better accountsfor the complex DNA-DNA interactions. We will develop that theory. The mainpart of this project is theoretical, but the predictions of the theory willbe tested against new experiments that will be performed in collaborationwith the named Project Partners.

Publications

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Lee D (2013) Chiral effects in dual-DNA braiding in Soft Matter

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Starostin E (2014) Theory of equilibria of elastic 2-braids with interstrand interaction in Journal of the Mechanics and Physics of Solids

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Starostin E (2014) Tightening elastic ( n , 2)-torus knots in Journal of Physics: Conference Series

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Starostin EL (2013) Condensation of circular DNA. in The Journal of chemical physics

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Starostin EL (2015) Characterisation of cylindrical curves. in Monatshefte fur Mathematik

 
Description We developed a mathematical model (elastic theory) of supercoiled DNA molecules. The model allows for interstrand interactions and is the first one not to make any assumptions on the shape of a supercoil; rather, this shape is found as part of the solution of the equations. A detailed continuum model for electrostatic DNA-DNA interactions was developed by the Imperial partner of this joint project. The combined theory was used to predict chiral (i.e., handedness) effects in DNA supercoiling. For instance we explained such chiral effects recently observed experimentally in the literature and hitherto unexplained. We also proposed new experiments where such effects might be more prominently seen in order to test the theory further.
Exploitation Route The theory is a general elastic theory of multi-strand structures and can also be applied to other biomolecules, polymers or other multi-strand structures (e.g., textile yarns, cables, etc.).
Sectors Education,Pharmaceuticals and Medical Biotechnology

 
Description In the design of biophysics experiments on DNA supercoiling.
First Year Of Impact 2012
Sector Education
 
Description Human Frontier Science Programme
Amount $1,200,000 (USD)
Funding ID RGP0049/2010 
Organisation Human Frontier Science Program (HFSP) 
Sector Charity/Non Profit
Country France
Start 06/2010 
End 05/2013
 
Description Biomolecular experiments (Baylor) 
Organisation Baylor College of Medicine
Country United States 
Sector Hospitals 
PI Contribution Mechanical modelling of DNA supercoiling, DNA topology
Collaborator Contribution Biomolecular experiments on DNA minicircles
Impact HFSP grant, 3 joint posters; multi-disciplinary: mechanics + molecular biology
Start Year 2010
 
Description Chiral DNA-DNA interactions (Imperial) 
Organisation Imperial College London
Department Department of Chemistry
Country United Kingdom 
Sector Academic/University 
PI Contribution Mechanical modelling of DNA supercoiling
Collaborator Contribution Physical/electrostatics modelling of DNA-DNA interaction.
Impact HFSP grant, 3 more joint research proposals, joint paper; multi-disciplinary: mechanics + chemistry
Start Year 2009
 
Description Dual-DNA supercoiling experiments (VU Amsterdam) 
Organisation Free University of Amsterdam
Country Netherlands 
Sector Academic/University 
PI Contribution Mechanical modelling of DNA supercoiling
Collaborator Contribution Dual-DNA experiments
Impact HFSP grant, 3 joint posters, joint research proposal; multi-disciplinary: mechanics + biophysics
Start Year 2010