RT Journal Article SR Electronic T1 Size-Dependent Accumulation of the Mitotic Activator Cdc25 as a Mechanism of Size Control in Fission Yeast JF bioRxiv FD Cold Spring Harbor Laboratory SP 078592 DO 10.1101/078592 A1 Daniel Keifenheim A1 Xi-Ming Sun A1 Edridge D’souza A1 Makoto Ohira A1 Mira Magner A1 Michael Mayhew A1 Samuel Marguerat A1 Nicholas Rhind YR 2016 UL http://biorxiv.org/content/early/2016/10/11/078592.abstract AB Proper cell size is essential for cellular function (Hall et al., 2004). Nonetheless, despite more than 100 years of work on the subject, the mechanisms that maintain cell size homeostasis are largely mysterious (Marshall et al., 2012). Cells in growing populations maintain cell size within a narrow range by coordinating growth and division. Bacterial and eukaryotic cells both demonstrate homeostatic size control, which maintains population-level variation in cell size within a certain range, and returns the population average to that range if it is perturbed (Marshall et al., 2012; Turner et al., 2012; Amodeo and Skotheim, 2015). Recent progress has revealed two different strategies for size control: budding yeast uses an inhibitor-dilution strategy to regulate size at the G1/S transition (Schmoller et al., 2015), while bacteria appear to use an adder strategy, in which a fixed amount of growth each generation causes cell size to converge on a stable average (Campos et al., 2014; Jun and Taheri-Araghi, 2015; Taheri-Araghi et al., 2015; Tanouchi et al., 2015). Here we present evidence that cell size in the fission yeast Schizosaccharomyces pombe is regulated by a third strategy: the size dependent accumulation of the mitotic activator Cdc25. Cdc25 is transcriptionally regulated such that smaller cells accumulate less Cdc25 and larger cells accumulate more Cdc25, creating an increasing concentration of Cdc25 as cell grow and providing a mechanism for cells to trigger cell division when they reach a threshold concentration of Cdc25. Since regulation of mitotic entry by Cdc25 is well conserved, this mechanism may provide a wide spread solution to the problem of size control in eukaryotes.