DNA-replication checkpoint control at the Drosophila midblastula transition

Embryogenesis is typically initiated by a series of rapid mitotic divisions that are under maternal genetic control(1). The switch to zygotic control of embryogenesis at the midblastula transition is accompanied by significant increases in cell-cycle length and gene transcription, and changes in embryo morphology(2,3). Here we show that mutations in the grapes (grp) checkpoint 1 kinase homologue(4) in Drosophila block the morphological and biochemical changes that accompany the midblastula transition, lead to a continuation of the maternal cell-cycle programme, and disrupt DNA-replication checkpoint control of cell-cycle progression. The timing of the midblastula transition is controlled by the ratio of nuclei to cytoplasm (the nucleocytoplasmic ratio), suggesting that this developmental transition is triggered by titration of a maternal factor by the increasing mass of nuclear material that accumulates during the rapid embryonic mitoses(5-9). Our observations support a model for cell-cycle control at the midblastula transition in which titration of a maternal component of the DNA-replication machinery slows DNA synthesis and induces a checkpoint-dependent delay in cell-cycle progression(10). This delay may allow both completion of S phase and transcription of genes that initiate the switch to zygotic control of embryogenesis.