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DNA-replication checkpoint control at the Drosophila midblastula transition

Nature volume 388, pages 93–97 (1997)Cite this article

Abstract

Embryogenesis is typically initiated by a series of rapid mitotic divisions that are under maternal genetic control1. 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 morphology2,3. Here we show that mutations in the grapes (grp) checkpoint 1 kinase homologue4 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 mitoses5,6,7,8,9. 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 progression10. This delay may allow both completion of S phase and transcription of genes that initiate the switch to zygotic control of embryogenesis.

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Figure 1: fs(A)4 mutant embryos fail to undergo changes in cell-cycle timing and embryo morphology associated with the MBT.
Figure 2: The fs(A)4 mutation prevents inhibitory tyrosine phosphorylation of Cdc2 and String phosphatase downregulation at the MBT.
Figure 3: Expression pattern of early zygotic transcripts is impaired in fs(A)4 mutants.
Figure 4: The grp gene is required to delay mitosis in response to the DNA-synthesis inhibitor aphidicolin.

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Acknowledgements

We thank W. Sullivan, S. Campbell, B. Holdener, J. Kramer, N. Hollingsworth and B. Eggen for comments on the manuscript; B. Edgar and P. O'Farrell for discussions; P. Gergen for probes and advice on whole-mount in situ hybridization; P. Fogarty and W. Sullivan for sharing unpublished data and providing grp cDNA clones; R. S. Hawley and colleagues at the University of California at Davis for providing their collection of P-element-associated maternal-effect lethal mutations; and B. Edgar for anti-Cdc2 antibodies and advice on cell-cycle control during early embryogenesis. This work was supported by a fellowship from the NWO to O.C.M.S. and grants from the NIH and American Cancer Society to W.E.T.

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  1. Department of Biochemistry and Cell Biology and the Institute for Cell and Developmental Biology, State University of New York at Stony Brook, Stony Brook, 11794-5215, New York, USA

    Ody C. M. Sibon, Victoria A. Stevenson & William E. Theurkauf

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  1. Ody C. M. Sibon
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Correspondence to William E. Theurkauf.

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Sibon, O., Stevenson, V. & Theurkauf, W. DNA-replication checkpoint control at the Drosophila midblastula transition. Nature 388, 93–97 (1997). https://doi.org/10.1038/40439

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