WEE1 opposes APC/C(CDH1) activity to promote S phase entry.

WEE1 promotes S phase entry by opposing APC/C(CDH1) activity through phosphorylation of CDH1.

• Why it matters: Understanding WEE1's functions beyond DNA damage checkpoints is crucial because WEE1 inhibitors show efficacy in both TP53-mutated and wild-type tumors but cause high toxicity, indicating unknown roles.
• What they did: The study used molecular and cellular approaches to demonstrate that WEE1 phosphorylates CDH1 at key residues, facilitating cell cycle re-entry from quiescence and affecting G1/S transition, with effects on p21 accumulation and G2 arrest.
• The result: Loss of WEE1 function delays S phase entry and increases G2 arrest, while reduced APC/C CDH1 or p21 expression enhances sensitivity to WEE1 inhibitors, suggesting new strategies for clinical application.