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The Grapes checkpoint coordinates nuclear envelope breakdown and chromosome condensation

Nature Cell Biology volume 2, pages 609–615 (2000)Cite this article

Abstract

Mutations in the embryonic Drosophila Grapes/Chk1 checkpoint result in an abbreviated interphase, chromosome condensation defects and metaphase delays. To clarify the relationship between these phenotypes, we simultaneously timed multiple nuclear and cytoplasmic events in mutant grp-derived embryos. These studies support a model in which grp disrupts an S-phase checkpoint, which results in progression into metaphase with incompletely replicated chromosomes. We also show that chromosome condensation is independent of the state of DNA replication in the early embryo. Therefore, grp condensation defects are not a direct consequence of entering metaphase with incompletely replicated chromosomes. Rather, initiation of chromosome condensation (ICC) occurs at the normal time in grp-derived embryos, but the shortened interval between ICC and metaphase does not provide sufficient time to complete condensation. Our results suggest that these condensation defects, rather than incomplete DNA replication, are responsible for the extensive metaphase delays observed in grp-derived embryos. This analysis provides an example of how the loss of a checkpoint can disrupt the timing of multiple events not directly monitored by that checkpoint. These results are likely to apply to vertebrate cells and suggest new strategies for destroying checkpoint-compromised cancer cells.

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Figure 1: Timing of the nuclear cycle.
Figure 2: The state of chromosome condensation during the cortical cycles of normal and grp-derived embryos.
Figure 3: Comparison of chromosome condensation in wild-type, grp-derived, and drug-treated embryos.
Figure 4: grp-derived embryos are sensitive to chromosome rearrangements.
Figure 5: Model explaining grp-induced metaphase delay.

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Acknowledgements

We thank J. Sisson, T. Su and S. Campbell for their critical reading of the manuscript and helpful discussions. We thank Tao-Shih Hsieh for providing VM26 and Arshad Desai for labelled histones. This work was supported by grants to W.S. from the National Institutes of Health (5R01 GM 46409-08), and to R.S. by the Australian Research Council (A09601106). Support for K.Y. was provided by a University of California Biotechnology Training Grant and an NIH Training grant (1T32GM0864601A1)

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  1. Department of Biology, University of California at Santa Cruz, Santa Cruz, 95064, California, USA

    Kristina R. Yu & William Sullivan

  2. Department of Genetics, University of Adelaide, Adelaide, SA 5005, South Australia, Australia

    Robert B. Saint

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Correspondence to William Sullivan.

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Yu, K., Saint, R. & Sullivan, W. The Grapes checkpoint coordinates nuclear envelope breakdown and chromosome condensation. Nat Cell Biol 2, 609–615 (2000). https://doi.org/10.1038/35023555

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