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dc.contributor.authorWunderlich, Zeba
dc.contributor.authorMirny, Leonid A.
dc.date.accessioned2012-09-20T13:07:14Z
dc.date.available2012-09-20T13:07:14Z
dc.date.issued2008-05
dc.date.submitted2008-03
dc.identifier.issn0305-1048
dc.identifier.issn1362-4962
dc.identifier.urihttp://hdl.handle.net/1721.1/73060
dc.description.abstractStrong experimental and theoretical evidence shows that transcription factors (TFs) and other specific DNA-binding proteins find their sites using a two-mode search: alternating between three-dimensional (3D) diffusion through the cell and one-dimensional (1D) sliding along the DNA. We show that, due to the 1D component of the search process, the search time of a TF can depend on the initial position of the TF. We formalize this effect by discriminating between two types of searches: global and local. Using analytical calculations and simulations, we estimate how close a TF and binding site need to be to make a local search likely. We then use our model to interpret the wide range of experimental measurements of this parameter. We also show that local and global searches differ significantly in average search time and the variability of search time. These results lead to a number of biological implications, including suggestions of how prokaryotes achieve rapid gene regulation and the relationship between the search mechanism and noise in gene expression. Lastly, we propose a number of experiments to verify the existence and quantify the extent of spatial effects on the TF search process in prokaryotes.en_US
dc.language.isoen_US
dc.publisherOxford University Press (OUP)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1093/nar/gkn173en_US
dc.rightsCreative Commons Attribution Non-Commercialen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc/2.5en_US
dc.sourceOxforden_US
dc.titleSpatial effects on the speed and reliability of protein–DNA searchen_US
dc.typeArticleen_US
dc.identifier.citationWunderlich, Z., and L. A. Mirny. “Spatial Effects on the Speed and Reliability of protein-DNA Search.” Nucleic Acids Research 36.11 (2008): 3570–3578.en_US
dc.contributor.departmentHarvard University--MIT Division of Health Sciences and Technologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Physicsen_US
dc.contributor.departmentMassachusetts Institute of Technology. School of Engineeringen_US
dc.contributor.mitauthorMirny, Leonid A.
dc.relation.journalNucleic Acids Researchen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsWunderlich, Z.; Mirny, L. A.en
dc.identifier.orcidhttps://orcid.org/0000-0002-0785-5410
mit.licensePUBLISHER_CCen_US


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