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Theoretical Analysis of the Stress Induced B-Z Transition in Superhelical DNA

We present a method to calculate the propensities of regions within a DNA molecule to transition from B-form to Z-form under negative superhelical stresses. We use statistical mechanics to analyze the competition that occurs among all susceptible Z-forming regions at thermodynamic equilibrium in a s...

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Autores principales: Zhabinskaya, Dina, Benham, Craig J.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024258/
https://www.ncbi.nlm.nih.gov/pubmed/21283778
http://dx.doi.org/10.1371/journal.pcbi.1001051
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author Zhabinskaya, Dina
Benham, Craig J.
author_facet Zhabinskaya, Dina
Benham, Craig J.
author_sort Zhabinskaya, Dina
collection PubMed
description We present a method to calculate the propensities of regions within a DNA molecule to transition from B-form to Z-form under negative superhelical stresses. We use statistical mechanics to analyze the competition that occurs among all susceptible Z-forming regions at thermodynamic equilibrium in a superhelically stressed DNA of specified sequence. This method, which we call SIBZ, is similar to the SIDD algorithm that was previously developed to analyze superhelical duplex destabilization. A state of the system is determined by assigning to each base pair either the B- or the Z-conformation, accounting for the dinucleotide repeat unit of Z-DNA. The free energy of a state is comprised of the nucleation energy, the sequence-dependent B-Z transition energy, and the energy associated with the residual superhelicity remaining after the change of twist due to transition. Using this information, SIBZ calculates the equilibrium B-Z transition probability of each base pair in the sequence. This can be done at any physiologically reasonable level of negative superhelicity. We use SIBZ to analyze a variety of representative genomic DNA sequences. We show that the dominant Z-DNA forming regions in a sequence can compete in highly complex ways as the superhelicity level changes. Despite having no tunable parameters, the predictions of SIBZ agree precisely with experimental results, both for the onset of transition in plasmids containing introduced Z-forming sequences and for the locations of Z-forming regions in genomic sequences. We calculate the transition profiles of 5 kb regions taken from each of 12,841 mouse genes and centered on the transcription start site (TSS). We find a substantial increase in the frequency of Z-forming regions immediately upstream from the TSS. The approach developed here has the potential to illuminate the occurrence of Z-form regions in vivo, and the possible roles this transition may play in biological processes.
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spelling pubmed-30242582011-01-31 Theoretical Analysis of the Stress Induced B-Z Transition in Superhelical DNA Zhabinskaya, Dina Benham, Craig J. PLoS Comput Biol Research Article We present a method to calculate the propensities of regions within a DNA molecule to transition from B-form to Z-form under negative superhelical stresses. We use statistical mechanics to analyze the competition that occurs among all susceptible Z-forming regions at thermodynamic equilibrium in a superhelically stressed DNA of specified sequence. This method, which we call SIBZ, is similar to the SIDD algorithm that was previously developed to analyze superhelical duplex destabilization. A state of the system is determined by assigning to each base pair either the B- or the Z-conformation, accounting for the dinucleotide repeat unit of Z-DNA. The free energy of a state is comprised of the nucleation energy, the sequence-dependent B-Z transition energy, and the energy associated with the residual superhelicity remaining after the change of twist due to transition. Using this information, SIBZ calculates the equilibrium B-Z transition probability of each base pair in the sequence. This can be done at any physiologically reasonable level of negative superhelicity. We use SIBZ to analyze a variety of representative genomic DNA sequences. We show that the dominant Z-DNA forming regions in a sequence can compete in highly complex ways as the superhelicity level changes. Despite having no tunable parameters, the predictions of SIBZ agree precisely with experimental results, both for the onset of transition in plasmids containing introduced Z-forming sequences and for the locations of Z-forming regions in genomic sequences. We calculate the transition profiles of 5 kb regions taken from each of 12,841 mouse genes and centered on the transcription start site (TSS). We find a substantial increase in the frequency of Z-forming regions immediately upstream from the TSS. The approach developed here has the potential to illuminate the occurrence of Z-form regions in vivo, and the possible roles this transition may play in biological processes. Public Library of Science 2011-01-20 /pmc/articles/PMC3024258/ /pubmed/21283778 http://dx.doi.org/10.1371/journal.pcbi.1001051 Text en Zhabinskaya, Benham. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Zhabinskaya, Dina
Benham, Craig J.
Theoretical Analysis of the Stress Induced B-Z Transition in Superhelical DNA
title Theoretical Analysis of the Stress Induced B-Z Transition in Superhelical DNA
title_full Theoretical Analysis of the Stress Induced B-Z Transition in Superhelical DNA
title_fullStr Theoretical Analysis of the Stress Induced B-Z Transition in Superhelical DNA
title_full_unstemmed Theoretical Analysis of the Stress Induced B-Z Transition in Superhelical DNA
title_short Theoretical Analysis of the Stress Induced B-Z Transition in Superhelical DNA
title_sort theoretical analysis of the stress induced b-z transition in superhelical dna
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024258/
https://www.ncbi.nlm.nih.gov/pubmed/21283778
http://dx.doi.org/10.1371/journal.pcbi.1001051
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