DNA-replication checkpoint control at the Drosophila midblastula transition

Nature. 1997 Jul 3;388(6637):93-7. doi: 10.1038/40439.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blastocyst
  • Cell Cycle / genetics
  • Cell Cycle / physiology
  • Cell Cycle Proteins
  • Checkpoint Kinase 1
  • Cyclin-Dependent Kinases / metabolism
  • DNA Replication*
  • Drosophila Proteins*
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / genetics*
  • Female
  • Genes, Insect
  • Genetic Complementation Test
  • Male
  • Mitosis / genetics
  • Mitosis / physiology
  • Mutation
  • Phosphoprotein Phosphatases / metabolism
  • Phosphorylation
  • Protein Tyrosine Phosphatases*
  • Protein-Serine-Threonine Kinases / genetics
  • Spindle Apparatus / genetics
  • Spindle Apparatus / physiology
  • Transcription, Genetic

Substances

  • Cell Cycle Proteins
  • Drosophila Proteins
  • Checkpoint Kinase 1
  • Protein-Serine-Threonine Kinases
  • grp protein, Drosophila
  • Cyclin-Dependent Kinases
  • Phosphoprotein Phosphatases
  • Protein Tyrosine Phosphatases
  • stg protein, Drosophila