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dc.contributor.authorEsadze, Alexandre
Kemme, Catherine A.
Kolomeisky, Anatoly B.
Iwahara, Junji
dc.date.accessioned 2014-10-09T15:38:23Z
dc.date.available 2014-10-09T15:38:23Z
dc.date.issued 2014
dc.identifier.citation Esadze, Alexandre, Kemme, Catherine A., Kolomeisky, Anatoly B., et al.. "Positive and negative impacts of nonspecific sites during target location by a sequence-specific DNA-binding protein: origin of the optimal search at physiological ionic strength." Nucleic Acids Research, 42, no. 11 (2014) Oxford University Press: 7039-7046. http://dx.doi.org/10.1093/nar/gku418.
dc.identifier.urihttps://hdl.handle.net/1911/77499
dc.description.abstract The inducible transcription factor Egr-1, which recognizes a 9-bp target DNA sequence via three zinc-finger domains, rapidly activates particular genes upon cellular stimuli such as neuronal signals and vascular stresses. Here, using the stopped-flow fluorescence method, we measured the target search kinetics of the Egr-1 zinc-finger protein at various ionic strengths between 40 and 400 mM KCl and found the most efficient search at 150 mM KCl. We further investigated the kinetics of intersegment transfer, dissociation, and sliding of this protein on DNA at distinct concentrations of KCl. Our data suggest that Egr-1's kinetic properties are well suited for efficient scanning of chromosomal DNA in vivo. Based on a newly developed theory, we analyzed the origin of the optimal search efficiency at physiological ionic strength. Target association is accelerated by nonspecific binding to nearby sites and subsequent sliding to the target as well as by intersegment transfer. Although these effects are stronger at lower ionic strengths, such conditions also favor trapping of the protein at distant nonspecific sites, decelerating the target association. Our data demonstrate that Egr-1 achieves the optimal search at physiological ionic strength through a compromise between the positive and negative impacts of nonspecific interactions with DNA.
dc.language.iso eng
dc.publisher Oxford University Press
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/
dc.title Positive and negative impacts of nonspecific sites during target location by a sequence-specific DNA-binding protein: origin of the optimal search at physiological ionic strength
dc.type Journal article
dc.contributor.funder American Heart Association
dc.contributor.funder Welch Foundation
dc.contributor.funder National Institutes of Health
dc.citation.journalTitle Nucleic Acids Research
dc.contributor.org Center for Theoretical Biological Physics
dc.citation.volumeNumber 42
dc.citation.issueNumber 11
dc.type.dcmi Text
dc.identifier.doihttp://dx.doi.org/10.1093/nar/gku418
dc.identifier.pmcid PMC4066804
dc.identifier.pmid 24838572
dc.identifier.grantID 12BGIA8960032 (American Heart Association)
dc.identifier.grantID C-1559 (Welch Foundation)
dc.identifier.grantID R01GM105931 (National Institutes of Health)
dc.identifier.grantID R01GM105931 (National Institutes of Health)
dc.type.publication publisher version
dc.citation.firstpage 7039
dc.citation.lastpage 7046


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