Cells Coordinate Growth and Proliferation

Cell size is a crucial factor in most fundamental processes, such as nutrient transport. In an abnormally large cell, nutrients have to move longer distances to spread throughout the cell. As a result, nutrient diffusion becomes slow, causing the cell to die from nutrient starvation.  Therefore, a healthy cell regulates its growth at cell cycle checkpoints- usually at the G1/S phase transition or the G2/M phase transition. These checkpoints enable the cell to monitor its size and regulate the timing of cell division, thereby ensuring the daughter cells have a consistent size- a phenomenon called size homeostasis. Unicellular organisms, such as yeast, are frequently used as model organisms to study size homeostasis. A budding yeast cell divides asymmetrically, producing a larger mother cell and a smaller daughter cell. The larger mother cell quickly grows to its critical size and passes the size checkpoint at the G1/S phase transition. In contrast, the smaller daughter cell has a large size gap to achieve and therefore spends more time growing in the G1 phase. At the early G1 phase, protein complexes SBF and MBF, the cell cycle-promoting transcription factors are usually bound and inhibited by a repressor protein called Whi5, thereby preventing cell cycle transition. The cell cycle reactivation depends on a sizer protein called Cln3, a G1 cyclin whose concentration increases proportionally with the cell size. When the cell attains its target size, Cln3 reaches a critical concentration and forms a complex with cyclin-dependent kinase-1 or Cdk1, a key activator of cell cycle promoting factors.  The active Cln3-Cdk1 complex then phosphorylates Whi5 at multiple sites to release active SBF and MBF transcription factors that trigger G1/S phase transition genes involved in vital processes such as bud initiation and DNA replication. Activation of these transition events enables the cell to pass the size checkpoint and proceed through other stages of the cell cycle.