In Drosophila, the nuclear divisions following fertilisation oscillate rapidly between S and M phases, with no growth phases or cytoplasmic cleavage. Metazoan development depends on correct cell-cycle control, but it remains unknown how DNA replication and mitosis are coordinated during such rapid divisions. On p. 449, Laura Lee and co-workers reveal that no poles(nopo), a gene encoding a putative ubiquitin ligase, is essential for the preservation of genomic integrity during these early stages of Drosophila development. The researchers find that nopomutant flies have misshapen spindles and undergo mitotic arrest, and that a mutation in the gene encoding the DNA checkpoint kinase CHK2 partially rescues these defects. Thus, the nopo phenotype is probably due to CHK2-mediated centrosome inactivation, a protective mechanism in flies that prevents nuclear division after DNA damage or incomplete replication. In addition, the researchers demonstrate that NOPO interacts with BEN, a ubiquitin-conjugating enzyme, leading them to propose that NOPO and BEN form a ubiquitin ligase complex that is required to prevent DNA defects during Drosophila embryogenesis.