Tuning Genetic Clocks Employing DNA Binding Sites
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...
| Main Authors: | , |
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2012
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| Online Access: | http://hdl.handle.net/1721.1/74639 https://orcid.org/0000-0001-6472-8576 |
| _version_ | 1811072485047664640 |
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| author | Del Vecchio, Domitilla Jayanthi, Shridhar |
| author2 | Massachusetts Institute of Technology. Department of Mechanical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Mechanical Engineering Del Vecchio, Domitilla Jayanthi, Shridhar |
| author_sort | Del Vecchio, Domitilla |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T09:06:42Z |
| format | Article |
| id | mit-1721.1/74639 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:06:42Z |
| publishDate | 2012 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/746392022-09-26T10:32:48Z Tuning Genetic Clocks Employing DNA Binding Sites Del Vecchio, Domitilla Jayanthi, Shridhar Massachusetts Institute of Technology. Department of Mechanical Engineering Del Vecchio, Domitilla Jayanthi, Shridhar 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. United States. Air Force Office of Scientific Research (Grant FA9550-09-1-0211) National Science Foundation (U.S.). (Communication and Information Foundations) (Grant 1058127) 2012-11-14T16:03:54Z 2012-11-14T16:03:54Z 2012-07 2012-01 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/74639 Jayanthi, Shridhar, and Domitilla Del Vecchio. “Tuning Genetic Clocks Employing DNA Binding Sites.” Ed. Mukund Thattai. PLoS ONE 7.7 (2012). https://orcid.org/0000-0001-6472-8576 en_US http://dx.doi.org/10.1371/journal.pone.0041019 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Del Vecchio, Domitilla Jayanthi, Shridhar Tuning Genetic Clocks Employing DNA Binding Sites |
| title | Tuning Genetic Clocks Employing DNA Binding Sites |
| title_full | Tuning Genetic Clocks Employing DNA Binding Sites |
| title_fullStr | Tuning Genetic Clocks Employing DNA Binding Sites |
| title_full_unstemmed | Tuning Genetic Clocks Employing DNA Binding Sites |
| title_short | Tuning Genetic Clocks Employing DNA Binding Sites |
| title_sort | tuning genetic clocks employing dna binding sites |
| url | http://hdl.handle.net/1721.1/74639 https://orcid.org/0000-0001-6472-8576 |
| work_keys_str_mv | AT delvecchiodomitilla tuninggeneticclocksemployingdnabindingsites AT jayanthishridhar tuninggeneticclocksemployingdnabindingsites |