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

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dc.citation.firstpage7039en_US
dc.citation.issueNumber11en_US
dc.citation.journalTitleNucleic Acids Researchen_US
dc.citation.lastpage7046en_US
dc.citation.volumeNumber42en_US
dc.contributor.authorEsadze, Alexandreen_US
dc.contributor.authorKemme, Catherine A.en_US
dc.contributor.authorKolomeisky, Anatoly B.en_US
dc.contributor.authorIwahara, Junjien_US
dc.contributor.orgCenter for Theoretical Biological Physicsen_US
dc.date.accessioned2014-10-09T15:38:23Zen_US
dc.date.available2014-10-09T15:38:23Zen_US
dc.date.issued2014en_US
dc.description.abstractThe 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.en_US
dc.identifier.citationEsadze, 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." <i>Nucleic Acids Research,</i> 42, no. 11 (2014) Oxford University Press: 7039-7046. http://dx.doi.org/10.1093/nar/gku418.en_US
dc.identifier.doihttp://dx.doi.org/10.1093/nar/gku418en_US
dc.identifier.urihttps://hdl.handle.net/1911/77499en_US
dc.language.isoengen_US
dc.publisherOxford University Pressen_US
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.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/en_US
dc.titlePositive and negative impacts of nonspecific sites during target location by a sequence-specific DNA-binding protein: origin of the optimal search at physiological ionic strengthen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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