Checkpoint kinase checks out Cdc25B

Cdc25 is an essential phosphatase that triggers cell-cycle progression by dephosphorylating (and thus activating) the central mitotic regulator cyclin-dependent kinase 1 (CDK1). Cdc25B activates a centrosomal pool of CDK1 prior to mitosis. CDK1 is thought to be held in check until then by the checkpoint kinase Chk1, but how Chk1 accomplishes this has not been clear. On p. 4269, Bernard Ducommun and co-workers reveal it does so by phosphorylating Cdc25B. They demonstrate that Chk1 phosphorylates several sites on Cdc25 in vitro, including S230. They then show that S230 of Cdc25B is phosphorylated in vivo in a cell-cycle-dependent manner. Furthermore, they use a specific Chk1 inhibitor and RNAi to show that this depends on Chk1. Finally, the authors show a non-phosphorylatable S230A mutant of Cdc25B, which presumably cannot be inhibited by Chk1, promotes premature entry of cells into mitosis. Ducommun and co-workers therefore conclude that Chk1 plays a role beyond its well-known function in the DNA damage response, proposing that it also constitutively phosphorylates Cdc25B during interphase to prevent premature entry into mitosis.