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Noisy Cell-Size-Correlated Expression of Cyclin B Drives Probabilistic Cell-Size Homeostasis in Fission Yeast

James O. Patterson, Paul Rees Orcid Logo, Paul Nurse

Current Biology, Volume: 29, Issue: 8, Pages: 1379 - 1386.e4

Swansea University Author: Paul Rees Orcid Logo

Abstract

How cells correct deviations from a mean cell size at mitosis remains uncertain. Classical cell-size homeostasis models are the sizer, timer, and adder [1]. Sizers postulate that cells divide at some threshold size; timers, that cells grow for a set time; and adders, that cells add a constant volume...

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Published in: Current Biology
ISSN: 0960-9822
Published: 2019
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URI: https://cronfa.swan.ac.uk/Record/cronfa50183
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spelling 2019-05-01T10:29:12.7896320 v2 50183 2019-05-01 Noisy Cell-Size-Correlated Expression of Cyclin B Drives Probabilistic Cell-Size Homeostasis in Fission Yeast 537a2fe031a796a3bde99679ee8c24f5 0000-0002-7715-6914 Paul Rees Paul Rees true false 2019-05-01 MEDE How cells correct deviations from a mean cell size at mitosis remains uncertain. Classical cell-size homeostasis models are the sizer, timer, and adder [1]. Sizers postulate that cells divide at some threshold size; timers, that cells grow for a set time; and adders, that cells add a constant volume before division. Here, we show that a size-based probabilistic model of cell-size control at the G2/M transition (P(Div)) can generate realistic cell-size homeostasis in silico. In fission yeast cells, Cyclin BCdc13 scales with size, and we propose that this increases the likelihood of mitotic entry, while molecular noise in its expression adds a probabilistic component to the model. Varying Cdc13 expression levels exogenously using a newly developed tetracycline inducible promoter shows that both the level and variability of its expression influence cell size at division. Our results demonstrate that as cells grow larger, their probability of dividing increases, and this is sufficient to generate cell-size homeostasis. Size-correlated Cdc13 expression forms part of the molecular circuitry of this system. Journal Article Current Biology 29 8 1379 1386.e4 0960-9822 31 12 2019 2019-12-31 10.1016/j.cub.2019.03.011 COLLEGE NANME Biomedical Engineering COLLEGE CODE MEDE Swansea University 2019-05-01T10:29:12.7896320 2019-05-01T10:26:55.4666594 Faculty of Science and Engineering School of Engineering and Applied Sciences - Biomedical Engineering James O. Patterson 1 Paul Rees 0000-0002-7715-6914 2 Paul Nurse 3 0050183-01052019102849.pdf patterson2019.pdf 2019-05-01T10:28:49.9930000 Output 3912173 application/pdf Version of Record true 2019-05-01T00:00:00.0000000 false eng
title Noisy Cell-Size-Correlated Expression of Cyclin B Drives Probabilistic Cell-Size Homeostasis in Fission Yeast
spellingShingle Noisy Cell-Size-Correlated Expression of Cyclin B Drives Probabilistic Cell-Size Homeostasis in Fission Yeast
Paul Rees
title_short Noisy Cell-Size-Correlated Expression of Cyclin B Drives Probabilistic Cell-Size Homeostasis in Fission Yeast
title_full Noisy Cell-Size-Correlated Expression of Cyclin B Drives Probabilistic Cell-Size Homeostasis in Fission Yeast
title_fullStr Noisy Cell-Size-Correlated Expression of Cyclin B Drives Probabilistic Cell-Size Homeostasis in Fission Yeast
title_full_unstemmed Noisy Cell-Size-Correlated Expression of Cyclin B Drives Probabilistic Cell-Size Homeostasis in Fission Yeast
title_sort Noisy Cell-Size-Correlated Expression of Cyclin B Drives Probabilistic Cell-Size Homeostasis in Fission Yeast
author_id_str_mv 537a2fe031a796a3bde99679ee8c24f5
author_id_fullname_str_mv 537a2fe031a796a3bde99679ee8c24f5_***_Paul Rees
author Paul Rees
author2 James O. Patterson
Paul Rees
Paul Nurse
format Journal article
container_title Current Biology
container_volume 29
container_issue 8
container_start_page 1379
publishDate 2019
institution Swansea University
issn 0960-9822
doi_str_mv 10.1016/j.cub.2019.03.011
college_str Faculty of Science and Engineering
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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 How cells correct deviations from a mean cell size at mitosis remains uncertain. Classical cell-size homeostasis models are the sizer, timer, and adder [1]. Sizers postulate that cells divide at some threshold size; timers, that cells grow for a set time; and adders, that cells add a constant volume before division. Here, we show that a size-based probabilistic model of cell-size control at the G2/M transition (P(Div)) can generate realistic cell-size homeostasis in silico. In fission yeast cells, Cyclin BCdc13 scales with size, and we propose that this increases the likelihood of mitotic entry, while molecular noise in its expression adds a probabilistic component to the model. Varying Cdc13 expression levels exogenously using a newly developed tetracycline inducible promoter shows that both the level and variability of its expression influence cell size at division. Our results demonstrate that as cells grow larger, their probability of dividing increases, and this is sufficient to generate cell-size homeostasis. Size-correlated Cdc13 expression forms part of the molecular circuitry of this system.
published_date 2019-12-31T04:01:32Z
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