Chiral theory of DNA supercoiling
Author(s)
Cortini, Ruggero
Type
Thesis
Abstract
DNA supercoiling is a fundamental biological process occurring in all cells. We
developed a theory of braiding (supercoiling) of a pair of DNA molecules that takes
into account the contribution of the bending and the electrostatic energy. The electrostatic
interaction was calculated within the framework of the Kornyshev-Leikin
theory of DNA interactions, which takes into account realistic helical patterns of
charge. Because of the chirality of the charge patterns, we predict that left-handed
braiding of a pair of DNA molecules is more favourable than right-handed braiding.
Applying our model to the case of closed loop DNA supercoiling and to single
molecule DNA micromanipulations, we predict novel effects that have not yet been
experimentally observed. We show that supercoiling may occur in topologically
relaxed plasmids, as a consequence of attractive chiral forces. We speculate about
the potential biological role of the predicted effects in the case of topoisomerase
action, and the occurrence of positively supercoiled DNA in hyperthermophilic
bacteria and archea. Our findings also suggest alternative an explanation of well-known
experiments that proved that divalent ions overwind DNA. We also give
an explanation for pairing of homologous DNA molecules in monovalent salt, and
explain the occurrence of tight supercoiling observed in cryo-electron and atomic
force microscopy. The analysis of existing experimental data shows that in most
cases the chiral effects that we predict remain elusive. The theory therefore awaits final experimental verification.
developed a theory of braiding (supercoiling) of a pair of DNA molecules that takes
into account the contribution of the bending and the electrostatic energy. The electrostatic
interaction was calculated within the framework of the Kornyshev-Leikin
theory of DNA interactions, which takes into account realistic helical patterns of
charge. Because of the chirality of the charge patterns, we predict that left-handed
braiding of a pair of DNA molecules is more favourable than right-handed braiding.
Applying our model to the case of closed loop DNA supercoiling and to single
molecule DNA micromanipulations, we predict novel effects that have not yet been
experimentally observed. We show that supercoiling may occur in topologically
relaxed plasmids, as a consequence of attractive chiral forces. We speculate about
the potential biological role of the predicted effects in the case of topoisomerase
action, and the occurrence of positively supercoiled DNA in hyperthermophilic
bacteria and archea. Our findings also suggest alternative an explanation of well-known
experiments that proved that divalent ions overwind DNA. We also give
an explanation for pairing of homologous DNA molecules in monovalent salt, and
explain the occurrence of tight supercoiling observed in cryo-electron and atomic
force microscopy. The analysis of existing experimental data shows that in most
cases the chiral effects that we predict remain elusive. The theory therefore awaits final experimental verification.
Date Issued
2012-11
Date Awarded
2013-02
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Kornyshev, Alexei
Sponsor
Engineering and Physical Sciences Research Council
Grant Number
EP/H004319/1
Publisher Department
Chemistry
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)