The Grapes checkpoint coordinates nuclear envelope breakdown and chromosome condensation

Mutations in the embryonic Drosophila Grapes/Chk1 checkpoint result in an a bbreviated interphase, chromosome condensation defects and metaphase delays . To clarify the relationship between these phenotypes, we simultaneously t imed 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 c hromosomes, 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 incompletel y replicated chromosomes. Rather, initiation of chromosome condensation (IC C) occurs at the normal time in grp-derived embryos, but the shortened inte rval 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 metaphas e 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 appl y to vertebrate cells and suggest new strategies for destroying checkpoint- compromised cancer cells.