The fission yeast cell size control system integrates pathways measuring cell surface area, volume, and time.

Eukaryotic cells tightly control their size, but the relevant aspect of size is unknown in most cases. Fission yeast divide at a threshold cell surface area (SA) due, in part, to the protein kinase Cdr2. We find that fission yeast cells only divide by SA under a size threshold. Mutants that divide at a larger size shift to volume-based divisions. Diploid cells divide at a larger size than haploid cells do, but they maintain SA-based divisions, and this indicates that the size threshold for changing from surface-area-based to volume-based control is set by ploidy. Within this size control system, we found that the mitotic activator Cdc25 accumulates like a volume-based sizer molecule, whereas the mitotic cyclin Cdc13 accumulates in the nucleus as a timer. We propose an integrated model for cell size control based on multiple signaling pathways that report on distinct aspects of cell size and growth, including cell SA (Cdr2), cell volume (Cdc25), and time (Cdc13). Combined modeling and experiments show how this system can generate both sizer- and adder-like properties. • The size and ploidy of fission yeast cells determine their size control strategy • Mitotic activator Cdc25 exhibits properties of a volume-based sizer molecule • Mitotic cyclin Cdc13 accumulates in the nucleus dependent on time and not size • Combined modeling and experiments show conditions for sizer versus adder behavior Miller et al. find that the fission yeast mitotic cyclin Cdc13 accumulates like a molecular timer, whereas the mitotic activator Cdc25 exhibits properties of a volume-based sizer protein. This study reveals an integrated cell size control network and provides insights into how cell cycle signals scale with cell size and growth for cell size control. [ABSTRACT FROM AUTHOR]