Abstract
Chk1 is required for arrest of the mammalian cell cycle before mitosis in response to DNA damage or replication block. It is also implicated in regulation of cell cycle progression because it is essential for embryonic cell viability. With the use of mouse embryonic stem cells conditionally deficient in Chk1, we now show that this kinase is indispensable for the timing of mitotic initiation. Chk1 deficiency resulted in premature onset of mitosis through reduction of Cdc2 phosphorylation on Tyr15 as a result of increased Cdc25 activity and decreased Wee1 activity. Our results suggest that Chk1 regulates Cdc2 to establish proper timing of mitotic initiation during the mammalian embryonic cell cycle.
