@article{1d9cce17294a4a29a00797c5eb0d6eb9,
title = "Noisy Cell-Size-Correlated Expression of Cyclin B Drives Probabilistic Cell-Size Homeostasis in Fission Yeast",
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 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 B Cdc13 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. ",
keywords = "CDK, cell division, cell growth, cell size, cyclin, cyclin-dependent kinase, mitosis, single-cell biology, systems biology",
author = "Patterson, {James O.} and Paul Rees and Paul Nurse",
note = "Funding Information: We thank S. Hauf for providing us with the Cdc13-sfGFP before publication and J. Greenwood, S. Basu, and H. Cantwell for critical reading of the manuscript. J.O.P. and P.R. acknowledge the support of the Biotechnology and Biological Sciences Research Council under grant BB/P026818/1. P.R. also acknowledges the support of the Biotechnology and Biological Sciences Research Council/ National Science Foundation under grant BB/N005163/1 and NSF DBI 1458626. J.O.P and P.N. acknowledge the support of the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC01121), the UK Medical Research Council (FC01121), and the Wellcome Trust (FC01121). This work was also supported by the Wellcome Trust (grant number 093917). P.N. acknowledges support from The Breast Cancer Research Foundation and The Lord Leonard and Lady Estelle Wolfson Foundation. J.O.P. acknowledges support from the Boehringer Ingelheim Fonds PhD fellowship. J.O.P. wrote the manuscript, designed the project, carried out the experiments, developed and performed microscopic image analyses, and developed the computational models. P.R. developed computational tools for Imagestream image analysis. P.N. supervised the project and co-wrote the manuscript. The authors declare no competing interests. Funding Information: We thank S. Hauf for providing us with the Cdc13-sfGFP before publication and J. Greenwood, S. Basu, and H. Cantwell for critical reading of the manuscript. J.O.P. and P.R. acknowledge the support of the Biotechnology and Biological Sciences Research Council under grant BB/P026818/1 . P.R. also acknowledges the support of the Biotechnology and Biological Sciences Research Council / National Science Foundation under grant BB/N005163/1 and NSF DBI 1458626 . J.O.P and P.N. acknowledge the support of the Francis Crick Institute, which receives its core funding from Cancer Research UK ( FC01121 ), the UK Medical Research Council ( FC01121 ), and the Wellcome Trust ( FC01121 ). This work was also supported by the Wellcome Trust (grant number 093917 ). P.N. acknowledges support from The Breast Cancer Research Foundation and The Lord Leonard and Lady Estelle Wolfson Foundation . J.O.P. acknowledges support from the Boehringer Ingelheim Fonds PhD fellowship. Publisher Copyright: {\textcopyright} 2019 The Authors",
year = "2019",
month = apr,
day = "22",
doi = "10.1016/j.cub.2019.03.011",
language = "English (US)",
volume = "29",
pages = "1379--1386.e4",
journal = "Current Biology",
issn = "0960-9822",
publisher = "Cell Press",
number = "8",
}