Preventing DNA re-replication--divergent safeguards in yeast and metazoa

Eukaryotes employ redundant mechanisms to limit the replication of genomic DNA to only once per cycle. These mechanisms prevent DNA re-replication by restricting the assembly of the pre-replication complex to the cell cycle stages of late mitosis and G1 phase so that the re-initiation of DNA replication cannot occur during S phase. Here we discuss the conserved yet divergent mechanisms of replication control employed in yeast and metazoan species, including a perspective on the newly uncovered role of the CUL-4 ubiquitin ligase as a central regulator of DNA replication in the nematode Caenorhabditis elegans.