Transcriptional regulation is a major controller of cell cycle transition dynamics.

DNA replication, mitosis and mitotic exit are critical transitions of the cell cycle which normally occur only once per cycle. A universal control mechanism was proposed for the regulation of mitotic entry in which Cdk helps its own activation through two positive feedback loops. Recent discoveries...

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Autores principales:	Alessandro Romanel, Lars Juhl Jensen, Luca Cardelli, Attila Csikász-Nagy
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8fbbe216d7a347c69b8832ad8c46fbb9
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spelling	oai:doaj.org-article:8fbbe216d7a347c69b8832ad8c46fbb92021-11-18T07:30:46ZTranscriptional regulation is a major controller of cell cycle transition dynamics.1932-620310.1371/journal.pone.0029716https://doaj.org/article/8fbbe216d7a347c69b8832ad8c46fbb92012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22238641/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203DNA replication, mitosis and mitotic exit are critical transitions of the cell cycle which normally occur only once per cycle. A universal control mechanism was proposed for the regulation of mitotic entry in which Cdk helps its own activation through two positive feedback loops. Recent discoveries in various organisms showed the importance of positive feedbacks in other transitions as well. Here we investigate if a universal control system with transcriptional regulation(s) and post-translational positive feedback(s) can be proposed for the regulation of all cell cycle transitions. Through computational modeling, we analyze the transition dynamics in all possible combinations of transcriptional and post-translational regulations. We find that some combinations lead to 'sloppy' transitions, while others give very precise control. The periodic transcriptional regulation through the activator or the inhibitor leads to radically different dynamics. Experimental evidence shows that in cell cycle transitions of organisms investigated for cell cycle dependent periodic transcription, only the inhibitor OR the activator is under cyclic control and never both of them. Based on these observations, we propose two transcriptional control modes of cell cycle regulation that either STOP or let the cycle GO in case of a transcriptional failure. We discuss the biological relevance of such differences.Alessandro RomanelAlessandro RomanelLars Juhl JensenLuca CardelliAttila Csikász-NagyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 1, p e29716 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alessandro Romanel Alessandro Romanel Lars Juhl Jensen Luca Cardelli Attila Csikász-Nagy Transcriptional regulation is a major controller of cell cycle transition dynamics.
description	DNA replication, mitosis and mitotic exit are critical transitions of the cell cycle which normally occur only once per cycle. A universal control mechanism was proposed for the regulation of mitotic entry in which Cdk helps its own activation through two positive feedback loops. Recent discoveries in various organisms showed the importance of positive feedbacks in other transitions as well. Here we investigate if a universal control system with transcriptional regulation(s) and post-translational positive feedback(s) can be proposed for the regulation of all cell cycle transitions. Through computational modeling, we analyze the transition dynamics in all possible combinations of transcriptional and post-translational regulations. We find that some combinations lead to 'sloppy' transitions, while others give very precise control. The periodic transcriptional regulation through the activator or the inhibitor leads to radically different dynamics. Experimental evidence shows that in cell cycle transitions of organisms investigated for cell cycle dependent periodic transcription, only the inhibitor OR the activator is under cyclic control and never both of them. Based on these observations, we propose two transcriptional control modes of cell cycle regulation that either STOP or let the cycle GO in case of a transcriptional failure. We discuss the biological relevance of such differences.
format	article
author	Alessandro Romanel Alessandro Romanel Lars Juhl Jensen Luca Cardelli Attila Csikász-Nagy
author_facet	Alessandro Romanel Alessandro Romanel Lars Juhl Jensen Luca Cardelli Attila Csikász-Nagy
author_sort	Alessandro Romanel
title	Transcriptional regulation is a major controller of cell cycle transition dynamics.
title_short	Transcriptional regulation is a major controller of cell cycle transition dynamics.
title_full	Transcriptional regulation is a major controller of cell cycle transition dynamics.
title_fullStr	Transcriptional regulation is a major controller of cell cycle transition dynamics.
title_full_unstemmed	Transcriptional regulation is a major controller of cell cycle transition dynamics.
title_sort	transcriptional regulation is a major controller of cell cycle transition dynamics.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/8fbbe216d7a347c69b8832ad8c46fbb9
work_keys_str_mv	AT alessandroromanel transcriptionalregulationisamajorcontrollerofcellcycletransitiondynamics AT alessandroromanel transcriptionalregulationisamajorcontrollerofcellcycletransitiondynamics AT larsjuhljensen transcriptionalregulationisamajorcontrollerofcellcycletransitiondynamics AT lucacardelli transcriptionalregulationisamajorcontrollerofcellcycletransitiondynamics AT attilacsikasznagy transcriptionalregulationisamajorcontrollerofcellcycletransitiondynamics
_version_	1718423359598886912

Transcriptional regulation is a major controller of cell cycle transition dynamics.

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