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Generalized facilitated diffusion model for DNA-binding proteins with search and recognition states

  • Transcription factors (TFs) such as the lac repressor find their target sequence on DNA at remarkably high rates. In the established Berg-von Hippel model for this search process, the TF alternates between three-dimensional diffusion in the bulk solution and one-dimensional sliding along the DNA chain. To overcome the so-called speed-stability paradox, in similar models the TF was considered as being present in two conformations (search state and recognition state) between which it switches stochastically. Combining both the facilitated diffusion model and alternating states, we obtain a generalized model. We explicitly treat bulk excursions for rodlike chains arranged in parallel and consider a simplified model for coiled DNA. Compared to previously considered facilitated diffusion models, corresponding to limiting cases of our generalized model, we surprisingly find a reduced target search rate. Moreover, at optimal conditions there is no longer an equipartition between the time spent by the protein on and off the DNA chain.

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Author:Maximilian Bauer, Ralf MetzlerORCiDGND
ISSN:0006-3495 (print)
Parent Title (English):Biophysical journal
Publisher:Cell Press
Place of publication:Cambridge
Document Type:Article
Year of first Publication:2012
Year of Completion:2012
Release Date:2017/03/26
First Page:2321
Last Page:2330
Funder:Academy of Finland
Organizational units:Mathematisch-Naturwissenschaftliche Fakultät / Institut für Physik und Astronomie
Peer Review:Referiert