Long-range correlations in the mechanics of small DNA circles under topological stress revealed by multi-scale simulation.
It is well established that gene regulation can be achieved through activator and repressor proteins that bind to DNA and switch particular genes on or off, and that complex metabolic networks determine the levels of transcription of a given gene at a given time. Using three complementary computational techniques to study the sequence-dependence of DNA denaturation within DNA minicircles, we have observed that whenever the ends of the DNA are constrained, information can be transferred over long distances directly by the transmission of mechanical stress through the DNA itself, without any requirement for external signalling factors. Our models combine atomistic molecular dynamics (MD) with coarse-grained simulations and statistical mechanical calculations to span three distinct spatial resolutions and timescale regimes. While they give a consensus view of the non-locality of sequence-dependent denaturation in highly bent and supercoiled DNA loops, each also reveals a unique aspect of long-range informational transfer that occurs as a result of restraining the DNA within the closed loop of the minicircles.
School of Physics and Astronomy, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, UK.|Theoretical and Computational Science Center (TaCS), Science Laboratory Building, Faculty of Science, King Mongkut's University of Technology Thonburi (KMUTT), 126 Pracha-Uthit Road, Bang Mod, Thrung Khru, Bangkok 10140, Thailand.
Thana
T
Sutthibutpong
Rudolf Peierls Centre for Theoretical Physics, University of Oxford, Parks Road, Oxford OX1 3PU, UK.
Christian
C
Matek
UC Davis Genome Centre, Health Sciences Drive, Davis, CA 95616, USA.
Craig
C
Benham
Department of Physics, São Paulo State University, Rua Cristovão, São José do Rio Preto, SP 15054-000, Brazil.
Gabriel G
GG
Slade
Department of Physics, Biological Physical Sciences Institute, University of York, York, YO10 5DD, UK.
Agnes
A
Noy
School of Pharmacy and Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
Charles
C
Laughton
Physical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ, UK.
Jonathan P
JP
K Doye
Rudolf Peierls Centre for Theoretical Physics, University of Oxford, Parks Road, Oxford OX1 3PU, UK.
Ard A
AA
Louis
School of Physics and Astronomy, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, UK s.a.harris@leeds.ac.uk.|Astbury Centre for Structural and Molecular Biology, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, UK.
Sarah A
SA
Harris
D000465:Algorithms; D003198:Computer Simulation; D004270:DNA, Circular / Q000737:chemistry*; D004278:DNA, Superhelical / Q000737:chemistry; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D013314:Stress, Mechanical
D004270:DNA, Circular; D004278:DNA, Superhelical
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