Wee1Mik1

Wee1Mik1 refers to the family of Wee1-like protein kinases, notably two members in the fission yeast Schizosaccharomyces pombe: Wee1 and Mik1. These kinases act as negative regulators of the G2 to M phase transition by inhibiting cyclin-dependent kinase activity through phosphorylation of the Tyr15 residue on Cdc2 (CDK1). This inhibitory phosphorylation reduces MPF (CDK1–cyclin) activity and delays mitosis, allowing cells to grow and to respond to DNA integrity signals. The opposing phosphatase Cdc25 removes this phosphate, promoting mitotic entry.

In S. pombe, Wee1 and Mik1 function largely in a redundant or partially overlapping manner. Wee1 is the primary contributor to Tyr15 phosphorylation, while Mik1 can reinforce or compensate for Wee1 function under certain conditions. The Wee1/Mik1 axis integrates signals from cell-cycle cues and DNA damage checkpoints to enforce a G2 arrest when replication is incomplete or damage is detected.

Regulation of Wee1/Mik1 involves multiple layers, including transcriptional control, phosphorylation, and subcellular localization, with checkpoint kinases such as those in ATR-like pathways modulating activity to ensure genome stability. In vertebrates, homologous enzymes such as Wee1 and Myt1 perform analogous roles in G2/M control, illustrating the conservation of this regulatory module across eukaryotes.

Clinically, Wee1 inhibitors are studied as cancer therapeutics to disrupt G2/M checkpoint control in tumor cells, potentially enhancing the effectiveness of DNA-damaging treatments. The Wee1/Mik1 concept thus encapsulates a conserved mechanism that links cell-cycle progression to genome integrity and therapeutic strategies.