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: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3409220?pdf=render |
| _version_ | 1818905603048734720 |
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| author | Shridhar Jayanthi Domitilla Del Vecchio |
| author_facet | Shridhar Jayanthi Domitilla Del Vecchio |
| author_sort | Shridhar Jayanthi |
| collection | DOAJ |
| 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 | 2024-12-19T21:25:57Z |
| format | Article |
| id | doaj.art-bc1e398d9f944c91a1096ecee5b646e3 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T21:25:57Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-bc1e398d9f944c91a1096ecee5b646e32022-12-21T20:05:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0177e4101910.1371/journal.pone.0041019Tuning genetic clocks employing DNA binding sites.Shridhar JayanthiDomitilla Del VecchioPeriodic 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.http://europepmc.org/articles/PMC3409220?pdf=render |
| spellingShingle | Shridhar Jayanthi Domitilla Del Vecchio Tuning genetic clocks employing DNA binding sites. PLoS ONE |
| 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://europepmc.org/articles/PMC3409220?pdf=render |
| work_keys_str_mv | AT shridharjayanthi tuninggeneticclocksemployingdnabindingsites AT domitilladelvecchio tuninggeneticclocksemployingdnabindingsites |