Evolution of opposing regulatory interactions underlies the emergence of eukaryotic cell cycle checkpoints

Abstract In eukaryotes the entry into mitosis is initiated by activation of cyclin-dependent kinases (CDKs), which in turn activate a large number of protein kinases to induce all mitotic processes. The general view is that kinases are active in mitosis and phosphatases turn them off in interphase....

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Rosa D. Hernansaiz-Ballesteros, Csenge Földi, Luca Cardelli, László G. Nagy, Attila Csikász-Nagy
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3d5157b4495846c49c1da2771ff85aae
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3d5157b4495846c49c1da2771ff85aae
record_format	dspace
spelling	oai:doaj.org-article:3d5157b4495846c49c1da2771ff85aae2021-12-02T15:49:31ZEvolution of opposing regulatory interactions underlies the emergence of eukaryotic cell cycle checkpoints10.1038/s41598-021-90384-32045-2322https://doaj.org/article/3d5157b4495846c49c1da2771ff85aae2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90384-3https://doaj.org/toc/2045-2322Abstract In eukaryotes the entry into mitosis is initiated by activation of cyclin-dependent kinases (CDKs), which in turn activate a large number of protein kinases to induce all mitotic processes. The general view is that kinases are active in mitosis and phosphatases turn them off in interphase. Kinases activate each other by cross- and self-phosphorylation, while phosphatases remove these phosphate groups to inactivate kinases. Crucial exceptions to this general rule are the interphase kinase Wee1 and the mitotic phosphatase Cdc25. Together they directly control CDK in an opposite way of the general rule of mitotic phosphorylation and interphase dephosphorylation. Here we investigate why this opposite system emerged and got fixed in almost all eukaryotes. Our results show that this reversed action of a kinase-phosphatase pair, Wee1 and Cdc25, on CDK is particularly suited to establish a stable G2 phase and to add checkpoints to the cell cycle. We show that all these regulators appeared together in LECA (Last Eukaryote Common Ancestor) and co-evolved in eukaryotes, suggesting that this twist in kinase-phosphatase regulation was a crucial step happening at the emergence of eukaryotes.Rosa D. Hernansaiz-BallesterosCsenge FöldiLuca CardelliLászló G. NagyAttila Csikász-NagyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rosa D. Hernansaiz-Ballesteros Csenge Földi Luca Cardelli László G. Nagy Attila Csikász-Nagy Evolution of opposing regulatory interactions underlies the emergence of eukaryotic cell cycle checkpoints
description	Abstract In eukaryotes the entry into mitosis is initiated by activation of cyclin-dependent kinases (CDKs), which in turn activate a large number of protein kinases to induce all mitotic processes. The general view is that kinases are active in mitosis and phosphatases turn them off in interphase. Kinases activate each other by cross- and self-phosphorylation, while phosphatases remove these phosphate groups to inactivate kinases. Crucial exceptions to this general rule are the interphase kinase Wee1 and the mitotic phosphatase Cdc25. Together they directly control CDK in an opposite way of the general rule of mitotic phosphorylation and interphase dephosphorylation. Here we investigate why this opposite system emerged and got fixed in almost all eukaryotes. Our results show that this reversed action of a kinase-phosphatase pair, Wee1 and Cdc25, on CDK is particularly suited to establish a stable G2 phase and to add checkpoints to the cell cycle. We show that all these regulators appeared together in LECA (Last Eukaryote Common Ancestor) and co-evolved in eukaryotes, suggesting that this twist in kinase-phosphatase regulation was a crucial step happening at the emergence of eukaryotes.
format	article
author	Rosa D. Hernansaiz-Ballesteros Csenge Földi Luca Cardelli László G. Nagy Attila Csikász-Nagy
author_facet	Rosa D. Hernansaiz-Ballesteros Csenge Földi Luca Cardelli László G. Nagy Attila Csikász-Nagy
author_sort	Rosa D. Hernansaiz-Ballesteros
title	Evolution of opposing regulatory interactions underlies the emergence of eukaryotic cell cycle checkpoints
title_short	Evolution of opposing regulatory interactions underlies the emergence of eukaryotic cell cycle checkpoints
title_full	Evolution of opposing regulatory interactions underlies the emergence of eukaryotic cell cycle checkpoints
title_fullStr	Evolution of opposing regulatory interactions underlies the emergence of eukaryotic cell cycle checkpoints
title_full_unstemmed	Evolution of opposing regulatory interactions underlies the emergence of eukaryotic cell cycle checkpoints
title_sort	evolution of opposing regulatory interactions underlies the emergence of eukaryotic cell cycle checkpoints
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3d5157b4495846c49c1da2771ff85aae
work_keys_str_mv	AT rosadhernansaizballesteros evolutionofopposingregulatoryinteractionsunderliestheemergenceofeukaryoticcellcyclecheckpoints AT csengefoldi evolutionofopposingregulatoryinteractionsunderliestheemergenceofeukaryoticcellcyclecheckpoints AT lucacardelli evolutionofopposingregulatoryinteractionsunderliestheemergenceofeukaryoticcellcyclecheckpoints AT laszlognagy evolutionofopposingregulatoryinteractionsunderliestheemergenceofeukaryoticcellcyclecheckpoints AT attilacsikasznagy evolutionofopposingregulatoryinteractionsunderliestheemergenceofeukaryoticcellcyclecheckpoints
_version_	1718385684507525120

Evolution of opposing regulatory interactions underlies the emergence of eukaryotic cell cycle checkpoints

Ejemplares similares