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

Scott Curran Orcid Logo, Gautam Dey, Paul Rees Orcid Logo, Paul Nurse

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

Swansea University Author: Paul Rees Orcid Logo

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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
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URI: https://cronfa.swan.ac.uk/Record/cronfa61167
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fullrecord <?xml version="1.0"?><rfc1807><datestamp>2022-10-06T16:05:08.4129067</datestamp><bib-version>v2</bib-version><id>61167</id><entry>2022-09-09</entry><title>A quantitative and spatial analysis of cell cycle regulators during the fission yeast cycle</title><swanseaauthors><author><sid>537a2fe031a796a3bde99679ee8c24f5</sid><ORCID>0000-0002-7715-6914</ORCID><firstname>Paul</firstname><surname>Rees</surname><name>Paul Rees</name><active>true</active><ethesisStudent>false</ethesisStudent></author></swanseaauthors><date>2022-09-09</date><deptcode>MEDE</deptcode><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 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.</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 &amp; .daf files) and raw data are available upon request to P.N.</notes><college>COLLEGE NANME</college><department>Biomedical Engineering</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>MEDE</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 MEDE 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 Biomedical Engineering COLLEGE CODE MEDE 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
issn 0027-8424
1091-6490
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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hierarchy_top_id facultyofscienceandengineering
hierarchy_top_title Faculty of Science and Engineering
hierarchy_parent_id facultyofscienceandengineering
hierarchy_parent_title Faculty of Science and Engineering
department_str School of Engineering and Applied Sciences - Biomedical Engineering{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Engineering and Applied Sciences - Biomedical 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 2022-09-06T04:19:48Z
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