Stochasticity Triggers Activation of the S-phase Checkpoint Pathway in Budding Yeast

In a complex and ever-changing environment, various signal transduction pathways mediate outside signals and stress to a living cell and its intracellular responses. Eukaryotic cells utilize the DNA synthesis phase (S-phase) checkpoint to respond to DNA damage and replication stress, and the activat...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Peijie Zhou, Xin Gao, Xiaoli Li, Linxi Li, Caoyuan Niu, Qi Ouyang, Huiqiang Lou, Tiejun Li, Fangting Li
Formato:	article
Lenguaje:	EN
Publicado:	American Physical Society 2021
Materias:	Physics QC1-999
Acceso en línea:	https://doaj.org/article/be6024750869433f98eae86303ca5f73
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:be6024750869433f98eae86303ca5f73
record_format	dspace
spelling	oai:doaj.org-article:be6024750869433f98eae86303ca5f732021-12-02T14:23:38ZStochasticity Triggers Activation of the S-phase Checkpoint Pathway in Budding Yeast10.1103/PhysRevX.11.0110042160-3308https://doaj.org/article/be6024750869433f98eae86303ca5f732021-01-01T00:00:00Zhttp://doi.org/10.1103/PhysRevX.11.011004http://doi.org/10.1103/PhysRevX.11.011004https://doaj.org/toc/2160-3308In a complex and ever-changing environment, various signal transduction pathways mediate outside signals and stress to a living cell and its intracellular responses. Eukaryotic cells utilize the DNA synthesis phase (S-phase) checkpoint to respond to DNA damage and replication stress, and the activation of the S-phase checkpoint defers the routine progression in the S phase. Through the analysis of microfluidic single-cell measurements, we find that the behavior of yeast cells exhibits bimodal distribution in the activation of the S-phase checkpoint, and the nonactivated portion of cells obeys the exponential decay law over time, the rate of which is dictated by HU dosage. Mathematical modeling and further experimental evidence from different mutant strains support the idea that the activation of the yeast S-phase checkpoint is a stochastic barrier-crossing process in a double-well system, where the barrier height is determined by both DNA replication stress and autophosphorylation of the key effector kinase Rad53. Our approach, as a novel methodology, is generally applicable to quantitative analysis of the signal transduction pathways at the single-cell level.Peijie ZhouXin GaoXiaoli LiLinxi LiCaoyuan NiuQi OuyangHuiqiang LouTiejun LiFangting LiAmerican Physical SocietyarticlePhysicsQC1-999ENPhysical Review X, Vol 11, Iss 1, p 011004 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Physics QC1-999
spellingShingle	Physics QC1-999 Peijie Zhou Xin Gao Xiaoli Li Linxi Li Caoyuan Niu Qi Ouyang Huiqiang Lou Tiejun Li Fangting Li Stochasticity Triggers Activation of the S-phase Checkpoint Pathway in Budding Yeast
description	In a complex and ever-changing environment, various signal transduction pathways mediate outside signals and stress to a living cell and its intracellular responses. Eukaryotic cells utilize the DNA synthesis phase (S-phase) checkpoint to respond to DNA damage and replication stress, and the activation of the S-phase checkpoint defers the routine progression in the S phase. Through the analysis of microfluidic single-cell measurements, we find that the behavior of yeast cells exhibits bimodal distribution in the activation of the S-phase checkpoint, and the nonactivated portion of cells obeys the exponential decay law over time, the rate of which is dictated by HU dosage. Mathematical modeling and further experimental evidence from different mutant strains support the idea that the activation of the yeast S-phase checkpoint is a stochastic barrier-crossing process in a double-well system, where the barrier height is determined by both DNA replication stress and autophosphorylation of the key effector kinase Rad53. Our approach, as a novel methodology, is generally applicable to quantitative analysis of the signal transduction pathways at the single-cell level.
format	article
author	Peijie Zhou Xin Gao Xiaoli Li Linxi Li Caoyuan Niu Qi Ouyang Huiqiang Lou Tiejun Li Fangting Li
author_facet	Peijie Zhou Xin Gao Xiaoli Li Linxi Li Caoyuan Niu Qi Ouyang Huiqiang Lou Tiejun Li Fangting Li
author_sort	Peijie Zhou
title	Stochasticity Triggers Activation of the S-phase Checkpoint Pathway in Budding Yeast
title_short	Stochasticity Triggers Activation of the S-phase Checkpoint Pathway in Budding Yeast
title_full	Stochasticity Triggers Activation of the S-phase Checkpoint Pathway in Budding Yeast
title_fullStr	Stochasticity Triggers Activation of the S-phase Checkpoint Pathway in Budding Yeast
title_full_unstemmed	Stochasticity Triggers Activation of the S-phase Checkpoint Pathway in Budding Yeast
title_sort	stochasticity triggers activation of the s-phase checkpoint pathway in budding yeast
publisher	American Physical Society
publishDate	2021
url	https://doaj.org/article/be6024750869433f98eae86303ca5f73
work_keys_str_mv	AT peijiezhou stochasticitytriggersactivationofthesphasecheckpointpathwayinbuddingyeast AT xingao stochasticitytriggersactivationofthesphasecheckpointpathwayinbuddingyeast AT xiaolili stochasticitytriggersactivationofthesphasecheckpointpathwayinbuddingyeast AT linxili stochasticitytriggersactivationofthesphasecheckpointpathwayinbuddingyeast AT caoyuanniu stochasticitytriggersactivationofthesphasecheckpointpathwayinbuddingyeast AT qiouyang stochasticitytriggersactivationofthesphasecheckpointpathwayinbuddingyeast AT huiqianglou stochasticitytriggersactivationofthesphasecheckpointpathwayinbuddingyeast AT tiejunli stochasticitytriggersactivationofthesphasecheckpointpathwayinbuddingyeast AT fangtingli stochasticitytriggersactivationofthesphasecheckpointpathwayinbuddingyeast
_version_	1718391447952031744

Stochasticity Triggers Activation of the S-phase Checkpoint Pathway in Budding Yeast

Ejemplares similares