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. 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. Here we show that mutations in the grapes (grp) checkpoint 1 kinase homologue 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. 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. This delay may allow both completion of S phase and transcription of genes that initiate the switch to zygotic control of embryogenesis.
Sibon
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OC
Department of Biochemistry and Cell Biology, State University of New York at Stony Brook, 11794-5215, USA.
Stevenson
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VA
Theurkauf
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WE
D000818:Animals; D001755:Blastocyst; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins; D000071877:Checkpoint Kinase 1; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004261:DNA Replication; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics*; D005260:Female; D017344:Genes, Insect; D005816:Genetic Complementation Test; D008297:Male; D008938:Mitosis / Q000235:genetics / Q000502:physiology; D009154:Mutation; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D017027:Protein Tyrosine Phosphatases; D008941:Spindle Apparatus / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic
D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D000071877:Checkpoint Kinase 1; D017346:Protein Serine-Threonine Kinases; C000605877:grp protein, Drosophila; D018844:Cyclin-Dependent Kinases; D010749:Phosphoprotein Phosphatases; D017027:Protein Tyrosine Phosphatases; C059217:stg protein, Drosophila