Replication licensing: oops! ... I did it again.

All eukaryotes use multiple controls to restrict DNA replication to once per cell cycle. Nevertheless, inactivation of a single gene, cul-4, causes massive re-replication in Caenorhabditis elegans. A novel study explains this dramatic phenotype by demonstrating that the CUL-4 E3 ligase simultaneously controls two critical licensing factors: CDT-1 and CDC-6.