Chk1 Inhibition of the Replication Factor Drf1 Guarantees Cell-Cycle Elongation at the Xenopus laevis Mid-blastula Transition

Abstract

The early cell divisions of many metazoan embryos are rapid and occur in the near absence of transcription. At the mid-blastula transition (MBT), the cell cycle elongates and several processes become established including the onset of bulk transcription and cell-cycle checkpoints. How these events are timed and coordinated is poorly understood. Here we show in $\textit{Xenopus laevis}$ that developmental activation of the checkpoint kinase Chk1 at the MBT results in the SCF$^\beta$$^{-TRCP}$-dependent degradation of a limiting replication initiation factor Drf1. Inhibition of Drf1 is the primary mechanism by which Chk1 blocks cell-cycle progression in the early embryo and is an essential function of Chk1 at the blastula-to-gastrula stage of development. This study defines the down-regulation of Drf1 as an important mechanism to coordinate the lengthening of the cell cycle and subsequent developmental processes.