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A quantitative and spatial analysis of cell cycle regulators during the fission yeast cycle
,
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...
| Published in: | Proceedings of the National Academy of Sciences |
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| ISSN: | 0027-8424 1091-6490 |
| Published: |
Proceedings of the National Academy of Sciences
2022
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa61167 |
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| 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. |
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| Item Description: |
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: |
Faculty of Science and Engineering |
| 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. 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. |
| Issue: |
36 |