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Preventing DNA Re-Replication: Divergent Safeguards in Yeast and Metazoa

Eukaryotes employ multiple 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 period of late mitosis and G1 phase so that 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.