Tuning Genetic Clocks Employing DNA Binding Sites
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Jayanthi-2012-Tuning Genetic Clock.pdf
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576.87 KB
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Author(s)
Del Vecchio, Domitilla
Jayanthi, Shridhar
Date Issued
July 2012
Journal
PLoS ONE
Publisher
Public Library of Science
Citation
Jayanthi, Shridhar, and Domitilla Del Vecchio. “Tuning Genetic Clocks Employing DNA Binding Sites.” Ed. Mukund Thattai. PLoS ONE 7.7 (2012).
Version
Final published version
Abstract
Periodic oscillations play a key role in cell physiology from the cell cycle to circadian clocks. The interplay of positive and negative feedback loops among genes and proteins is ubiquitous in these networks. Often, delays in a negative feedback loop and/or degradation rates are a crucial mechanism to obtain sustained oscillations. How does nature control delays and kinetic rates in feedback networks? Known mechanisms include proper selection of the number of steps composing a feedback loop and alteration of protease activity, respectively. Here, we show that a remarkably simple means to control both delays and effective kinetic rates is the employment of DNA binding sites. We illustrate this design principle on a widely studied activator-repressor clock motif, which is ubiquitous in natural systems. By suitably employing DNA target sites for the activator and/or the repressor, one can switch the clock “on” and “off” and precisely tune its period to a desired value. Our study reveals a design principle to engineer dynamic behavior in biomolecular networks, which may be largely exploited by natural systems and employed for the rational design of synthetic circuits.
MIT Department
Massachusetts Institute of Technology. Department of Mechanical Engineering
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Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.1371/journal.pone.0041019
