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 deter- mine the levels of transcription of a given gene at a given time. Using three complementary computa-...

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Main Authors: Sutthibutpong, Thana, Matek, Matek, Benham, Craig, Slade, Gabriel G., Noy, Agnes, Laughton, Charles A., Doye, Jonathan P.K., Louis, Ard A., Harris, Sarah A.
Format: Article
Published: Oxford University Press 2016
Online Access:https://eprints.nottingham.ac.uk/42944/
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author Sutthibutpong, Thana
Matek, Matek
Benham, Craig
Slade, Gabriel G.
Noy, Agnes
Laughton, Charles A.
Doye, Jonathan P.K.
Louis, Ard A.
Harris, Sarah A.
author_facet Sutthibutpong, Thana
Matek, Matek
Benham, Craig
Slade, Gabriel G.
Noy, Agnes
Laughton, Charles A.
Doye, Jonathan P.K.
Louis, Ard A.
Harris, Sarah A.
author_sort Sutthibutpong, Thana
building Nottingham Research Data Repository
collection Online Access
description 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 deter- mine the levels of transcription of a given gene at a given time. Using three complementary computa- tional techniques to study the sequence-dependence of DNA denaturation within DNA minicircles, we have observed that whenever the ends of the DNA are con- strained, information can be transferred over long distances directly by the transmission of mechanical stress through the DNA itself, without any require- ment for external signalling factors. Our models com- bine atomistic molecular dynamics (MD) with coarse- grained simulations and statistical mechanical calcu- lations to span three distinct spatial resolutions and timescale regimes. While they give a consensus view of the non-locality of sequence-dependent denatura- tion in highly bent and supercoiled DNA loops, each also reveals a unique aspect of long-range informa- tional transfer that occurs as a result of restraining the DNA within the closed loop of the minicircles.
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publishDate 2016
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spelling nottingham-429442020-05-04T18:10:05Z https://eprints.nottingham.ac.uk/42944/ Long-range correlations in the mechanics of small DNA circles under topological stress revealed by multi-scale simulation Sutthibutpong, Thana Matek, Matek Benham, Craig Slade, Gabriel G. Noy, Agnes Laughton, Charles A. Doye, Jonathan P.K. Louis, Ard A. Harris, Sarah A. 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 deter- mine the levels of transcription of a given gene at a given time. Using three complementary computa- tional techniques to study the sequence-dependence of DNA denaturation within DNA minicircles, we have observed that whenever the ends of the DNA are con- strained, information can be transferred over long distances directly by the transmission of mechanical stress through the DNA itself, without any require- ment for external signalling factors. Our models com- bine atomistic molecular dynamics (MD) with coarse- grained simulations and statistical mechanical calcu- lations to span three distinct spatial resolutions and timescale regimes. While they give a consensus view of the non-locality of sequence-dependent denatura- tion in highly bent and supercoiled DNA loops, each also reveals a unique aspect of long-range informa- tional transfer that occurs as a result of restraining the DNA within the closed loop of the minicircles. Oxford University Press 2016-09-22 Article PeerReviewed Sutthibutpong, Thana, Matek, Matek, Benham, Craig, Slade, Gabriel G., Noy, Agnes, Laughton, Charles A., Doye, Jonathan P.K., Louis, Ard A. and Harris, Sarah A. (2016) Long-range correlations in the mechanics of small DNA circles under topological stress revealed by multi-scale simulation. Nucleic Acids Research, 44 (19). pp. 9121-9130. ISSN 1362-4962 https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkw815 doi:10.1093/nar/gkw815 doi:10.1093/nar/gkw815
spellingShingle Sutthibutpong, Thana
Matek, Matek
Benham, Craig
Slade, Gabriel G.
Noy, Agnes
Laughton, Charles A.
Doye, Jonathan P.K.
Louis, Ard A.
Harris, Sarah A.
Long-range correlations in the mechanics of small DNA circles under topological stress revealed by multi-scale simulation
title Long-range correlations in the mechanics of small DNA circles under topological stress revealed by multi-scale simulation
title_full Long-range correlations in the mechanics of small DNA circles under topological stress revealed by multi-scale simulation
title_fullStr Long-range correlations in the mechanics of small DNA circles under topological stress revealed by multi-scale simulation
title_full_unstemmed Long-range correlations in the mechanics of small DNA circles under topological stress revealed by multi-scale simulation
title_short Long-range correlations in the mechanics of small DNA circles under topological stress revealed by multi-scale simulation
title_sort long-range correlations in the mechanics of small dna circles under topological stress revealed by multi-scale simulation
url https://eprints.nottingham.ac.uk/42944/
https://eprints.nottingham.ac.uk/42944/
https://eprints.nottingham.ac.uk/42944/