Cdr1Cdr2

Cdr1 and Cdr2 are protein kinases in the fission yeast Schizosaccharomyces pombe that together regulate the timing of mitotic entry and the cell size at which cells divide. They belong to the SAD family of serine/threonine kinases and function as a core module in the control of the G2/M transition.

Cdr2 localizes to medial cortical nodes during interphase, where it acts as a scaffold to recruit Cdr1 to these cortical structures. Once at the nodes, Cdr1 becomes activated and inhibits Wee1, a kinase that keeps Cdc2 (Cdk1) in an inactive state by phosphorylating it. By inhibiting Wee1, Cdr1 promotes dephosphorylation and activation of Cdc2, enabling entry into mitosis via the Cdc25-mediated activation pathway.

The activity of Cdr1 and Cdr2 is integrated with cell size sensing through the Pom1 kinase gradient. Pom1 forms a concentration gradient emanating from the cell tips and inhibits Cdr2 at smaller cell sizes, delaying mitosis. As the cell grows and the Pom1 gradient diminishes at the medial cortex, Cdr2 activity increases, facilitating Cdr1 recruitment and Wee1 inhibition, thereby triggering mitotic entry at an appropriate cell size.

Beyond their roles in Wee1 regulation, Cdr1 and Cdr2 influence the organization of cortical nodes and participate in broader cell cycle control networks. Mutations or deletions in cdr1 or cdr2 can disrupt normal cell size at division and alter the timing of mitosis, underscoring their importance in coordinating growth with division.