A quantitative and spatial analysis of cell cycle regulators during the fission yeast cycle

Curran, Scott; Dey, Gautam; Rees, Paul; Nurse, Paul

doi:10.1073/pnas.2206172119

Journal article 847 views 173 downloads

A quantitative and spatial analysis of cell cycle regulators during the fission yeast cycle

Scott Curran

, Gautam Dey, Paul Rees

, Paul Nurse

Proceedings of the National Academy of Sciences, Volume: 119, Issue: 36

Swansea University Author: Paul Rees

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DOI (Published version): 10.1073/pnas.2206172119

Abstract

We have carried out a systems-level analysis of the spatial and temporal dynamics of cell cycle regulators in the fission yeast Schizosaccharomyces pombe. In a comprehensive single-cell analysis, we have precisely quantified the levels of 38 proteins previously identified as regulators of the G2 to...

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Published in:	Proceedings of the National Academy of Sciences
ISSN:	0027-8424 1091-6490
Published:	Proceedings of the National Academy of Sciences 2022
Online Access:	Check full text
URI:	https://cronfa.swan.ac.uk/Record/cronfa61167

first_indexed	2022-10-06T15:03:04Z
last_indexed	2023-01-13T19:21:46Z
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Only 2 of the 38 mitotic regulators exhibit changes in concentration at the whole-cell level: the mitotic B-type cyclin Cdc13, which accumulates continually throughout the cell cycle, and the regulatory phosphatase Cdc25, which exhibits a complex cell cycle pattern. Both proteins show similar patterns of change within the nucleus as in the whole cell but at higher concentrations. In addition, the concentrations of the major fission yeast cyclin-dependent kinase (CDK) Cdc2, the CDK regulator Suc1, and the inhibitory kinase Wee1 also increase in the nucleus, peaking at mitotic onset, but are constant in the whole cell. The significant increase in concentration with size for Cdc13 supports the view that mitotic B-type cyclin accumulation could act as a cell size sensor. We propose a two-step process for the control of mitosis. First, Cdc13 accumulates in a size-dependent manner, which drives increasing CDK activity. Second, from mid-G2, the increasing nuclear accumulation of Cdc25 and the counteracting Wee1 introduce a bistability switch that results in a rapid rise of CDK activity at the end of G2 and thus, brings about an orderly progression into mitosis.</abstract><type>Journal Article</type><journal>Proceedings of the National Academy of Sciences</journal><volume>119</volume><journalNumber>36</journalNumber><paginationStart/><paginationEnd/><publisher>Proceedings of the National Academy of Sciences</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint>0027-8424</issnPrint><issnElectronic>1091-6490</issnElectronic><keywords/><publishedDay>6</publishedDay><publishedMonth>9</publishedMonth><publishedYear>2022</publishedYear><publishedDate>2022-09-06</publishedDate><doi>10.1073/pnas.2206172119</doi><url/><notes>Data, Materials, and Software Availability. Processed data used for the plots in the main figures have been deposited to GitHub (https://github.com/scottcurran10/fission-yeast-cell-cycle/SOURCE DATA_CurranS_PNAS_2022) (57). Widefield microscopy images, Imagestream files (including .cif, .rif & .daf files) and raw data are available upon request to P.N.</notes><college>COLLEGE NANME</college><department>Engineering and Applied Sciences School</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>EAAS</DepartmentCode><institution>Swansea University</institution><apcterm/><funders>Thomas Hammond, Emma Roberts, and Theresa Zeisner and previous member Tiffany Mak for critical reading of the manuscript and comments. S.C. and P.N. were supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK Grant FC01121, UK Medical Research Council Grant FC01121, and Wellcome Trust Grant FC01121. In addition, this work was supported by Wellcome Trust Grants 214183 (to P.N.) and 093917 (to P.N.). G.D. acknowledges University College London, Wellcome Trust Grant 203276/Z/16/Z, and the European Molecular Biology Laboratory for support. 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spelling	2022-10-06T16:05:08.4129067 v2 61167 2022-09-09 A quantitative and spatial analysis of cell cycle regulators during the fission yeast cycle 537a2fe031a796a3bde99679ee8c24f5 0000-0002-7715-6914 Paul Rees Paul Rees true false 2022-09-09 EAAS We have carried out a systems-level analysis of the spatial and temporal dynamics of cell cycle regulators in the fission yeast Schizosaccharomyces pombe. In a comprehensive single-cell analysis, we have precisely quantified the levels of 38 proteins previously identified as regulators of the G2 to mitosis transition and of 7 proteins acting at the G1- to S-phase transition. Only 2 of the 38 mitotic regulators exhibit changes in concentration at the whole-cell level: the mitotic B-type cyclin Cdc13, which accumulates continually throughout the cell cycle, and the regulatory phosphatase Cdc25, which exhibits a complex cell cycle pattern. Both proteins show similar patterns of change within the nucleus as in the whole cell but at higher concentrations. In addition, the concentrations of the major fission yeast cyclin-dependent kinase (CDK) Cdc2, the CDK regulator Suc1, and the inhibitory kinase Wee1 also increase in the nucleus, peaking at mitotic onset, but are constant in the whole cell. The significant increase in concentration with size for Cdc13 supports the view that mitotic B-type cyclin accumulation could act as a cell size sensor. We propose a two-step process for the control of mitosis. First, Cdc13 accumulates in a size-dependent manner, which drives increasing CDK activity. Second, from mid-G2, the increasing nuclear accumulation of Cdc25 and the counteracting Wee1 introduce a bistability switch that results in a rapid rise of CDK activity at the end of G2 and thus, brings about an orderly progression into mitosis. Journal Article Proceedings of the National Academy of Sciences 119 36 Proceedings of the National Academy of Sciences 0027-8424 1091-6490 6 9 2022 2022-09-06 10.1073/pnas.2206172119 Data, Materials, and Software Availability. Processed data used for the plots in the main figures have been deposited to GitHub (https://github.com/scottcurran10/fission-yeast-cell-cycle/SOURCE DATA_CurranS_PNAS_2022) (57). Widefield microscopy images, Imagestream files (including .cif, .rif & .daf files) and raw data are available upon request to P.N. COLLEGE NANME Engineering and Applied Sciences School COLLEGE CODE EAAS Swansea University Thomas Hammond, Emma Roberts, and Theresa Zeisner and previous member Tiffany Mak for critical reading of the manuscript and comments. S.C. and P.N. were supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK Grant FC01121, UK Medical Research Council Grant FC01121, and Wellcome Trust Grant FC01121. In addition, this work was supported by Wellcome Trust Grants 214183 (to P.N.) and 093917 (to P.N.). G.D. acknowledges University College London, Wellcome Trust Grant 203276/Z/16/Z, and the European Molecular Biology Laboratory for support. P.R. acknowledges the support of Biotechnology and Biological Sciences Research Council Grant BB/P026818/1 and Engineering and Physical Science Research Council Grant EP/ N013506/1. 2022-10-06T16:05:08.4129067 2022-09-09T14:30:39.1139715 Faculty of Science and Engineering School of Engineering and Applied Sciences - Biomedical Engineering Scott Curran 0000-0002-7996-8764 1 Gautam Dey 2 Paul Rees 0000-0002-7715-6914 3 Paul Nurse 4 61167__25339__bea80d5fcecb4729aa7c01aed935a24f.pdf 61167_VoR.pdf 2022-10-06T16:03:29.6098620 Output 3551566 application/pdf Version of Record true Copyright © 2022 the Author(s). This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) true eng https://creativecommons.org/licenses/by/4.0/
title	A quantitative and spatial analysis of cell cycle regulators during the fission yeast cycle
spellingShingle	A quantitative and spatial analysis of cell cycle regulators during the fission yeast cycle Paul Rees
title_short	A quantitative and spatial analysis of cell cycle regulators during the fission yeast cycle
title_full	A quantitative and spatial analysis of cell cycle regulators during the fission yeast cycle
title_fullStr	A quantitative and spatial analysis of cell cycle regulators during the fission yeast cycle
title_full_unstemmed	A quantitative and spatial analysis of cell cycle regulators during the fission yeast cycle
title_sort	A quantitative and spatial analysis of cell cycle regulators during the fission yeast cycle
author_id_str_mv	537a2fe031a796a3bde99679ee8c24f5
author_id_fullname_str_mv	537a2fe031a796a3bde99679ee8c24f5_***_Paul Rees
author	Paul Rees
author2	Scott Curran Gautam Dey Paul Rees Paul Nurse
format	Journal article
container_title	Proceedings of the National Academy of Sciences
container_volume	119
container_issue	36
publishDate	2022
institution	Swansea University
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doi_str_mv	10.1073/pnas.2206172119
publisher	Proceedings of the National Academy of Sciences
college_str	Faculty of Science and Engineering
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description	We have carried out a systems-level analysis of the spatial and temporal dynamics of cell cycle regulators in the fission yeast Schizosaccharomyces pombe. In a comprehensive single-cell analysis, we have precisely quantified the levels of 38 proteins previously identified as regulators of the G2 to mitosis transition and of 7 proteins acting at the G1- to S-phase transition. Only 2 of the 38 mitotic regulators exhibit changes in concentration at the whole-cell level: the mitotic B-type cyclin Cdc13, which accumulates continually throughout the cell cycle, and the regulatory phosphatase Cdc25, which exhibits a complex cell cycle pattern. Both proteins show similar patterns of change within the nucleus as in the whole cell but at higher concentrations. In addition, the concentrations of the major fission yeast cyclin-dependent kinase (CDK) Cdc2, the CDK regulator Suc1, and the inhibitory kinase Wee1 also increase in the nucleus, peaking at mitotic onset, but are constant in the whole cell. The significant increase in concentration with size for Cdc13 supports the view that mitotic B-type cyclin accumulation could act as a cell size sensor. We propose a two-step process for the control of mitosis. First, Cdc13 accumulates in a size-dependent manner, which drives increasing CDK activity. Second, from mid-G2, the increasing nuclear accumulation of Cdc25 and the counteracting Wee1 introduce a bistability switch that results in a rapid rise of CDK activity at the end of G2 and thus, brings about an orderly progression into mitosis.
published_date	2022-09-06T05:05:43Z
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score	11.089572

A quantitative and spatial analysis of cell cycle regulators during the fission yeast cycle

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