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The ups and downs of biological timers

BACKGROUND: The need to execute a sequence of events in an orderly and timely manner is central to many biological processes, including cell cycle progression and cell differentiation. For self-perpetuating systems, such as the cell cycle oscillator, delay times between events are defined by the net...

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Autores principales: Rappaport, Noa, Winter, Shay, Barkai, Naama
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1208956/
https://www.ncbi.nlm.nih.gov/pubmed/15967029
http://dx.doi.org/10.1186/1742-4682-2-22
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author Rappaport, Noa
Winter, Shay
Barkai, Naama
author_facet Rappaport, Noa
Winter, Shay
Barkai, Naama
author_sort Rappaport, Noa
collection PubMed
description BACKGROUND: The need to execute a sequence of events in an orderly and timely manner is central to many biological processes, including cell cycle progression and cell differentiation. For self-perpetuating systems, such as the cell cycle oscillator, delay times between events are defined by the network of interacting proteins that propagates the system. However, protein levels inside cells are subject to genetic and environmental fluctuations, raising the question of how reliable timing is maintained. RESULTS: We compared the robustness of different mechanisms for encoding delay times to fluctuations in protein expression levels. Gradual accumulation and gradual decay of a regulatory protein have an equivalent capacity for defining delay times. Yet, we find that the former is highly sensitive to fluctuations in gene dosage, while the latter can buffer such perturbations. In particular, a positive feedback where the degrading protein auto-enhances its own degradation may render delay times practically insensitive to gene dosage. CONCLUSION: While our understanding of biological timing mechanisms is still rudimentary, it is clear that there is an ample use of degradation as well as self-enhanced degradation in processes such as cell cycle and circadian clocks. We propose that degradation processes, and specifically self-enhanced degradation, will be preferred in processes where maintaining the robustness of timing is important.
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spelling pubmed-12089562005-09-16 The ups and downs of biological timers Rappaport, Noa Winter, Shay Barkai, Naama Theor Biol Med Model Research BACKGROUND: The need to execute a sequence of events in an orderly and timely manner is central to many biological processes, including cell cycle progression and cell differentiation. For self-perpetuating systems, such as the cell cycle oscillator, delay times between events are defined by the network of interacting proteins that propagates the system. However, protein levels inside cells are subject to genetic and environmental fluctuations, raising the question of how reliable timing is maintained. RESULTS: We compared the robustness of different mechanisms for encoding delay times to fluctuations in protein expression levels. Gradual accumulation and gradual decay of a regulatory protein have an equivalent capacity for defining delay times. Yet, we find that the former is highly sensitive to fluctuations in gene dosage, while the latter can buffer such perturbations. In particular, a positive feedback where the degrading protein auto-enhances its own degradation may render delay times practically insensitive to gene dosage. CONCLUSION: While our understanding of biological timing mechanisms is still rudimentary, it is clear that there is an ample use of degradation as well as self-enhanced degradation in processes such as cell cycle and circadian clocks. We propose that degradation processes, and specifically self-enhanced degradation, will be preferred in processes where maintaining the robustness of timing is important. BioMed Central 2005-06-20 /pmc/articles/PMC1208956/ /pubmed/15967029 http://dx.doi.org/10.1186/1742-4682-2-22 Text en Copyright © 2005 Rappaport et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Rappaport, Noa
Winter, Shay
Barkai, Naama
The ups and downs of biological timers
title The ups and downs of biological timers
title_full The ups and downs of biological timers
title_fullStr The ups and downs of biological timers
title_full_unstemmed The ups and downs of biological timers
title_short The ups and downs of biological timers
title_sort ups and downs of biological timers
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1208956/
https://www.ncbi.nlm.nih.gov/pubmed/15967029
http://dx.doi.org/10.1186/1742-4682-2-22
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