Replication licensing ensures that DNA replication occurs exactly once per eukaryotic cell cycle. Licensing is achieved by sequentially loading replication-initiation proteins onto replication origins to form pre-replicative complexes (pre-RCs). Phosphorylation of initiation proteins by cyclin-dependent kinases (CDKs) prevents unscheduled replication licensing, but it is unclear whether phosphatases help to reset replication competency. Now, Chun Liang and colleagues (p. 3933) show that cell division cycle protein 14 (Cdc14p) – a phosphatase that helps to orchestrate mitotic exit – dephosphorylates several replication-initiation proteins to restore their competence for pre-RC assembly in budding yeast. Cells without functional Cdc14p, the authors report, fail to dephosphorylate initiation proteins, form pre-RCs or replicate DNA in mitotic rereplication systems. Conversely, pulsed ectopic expression of Cdc14p in mitotic cells results in efficient pre-RC assembly and DNA replication. Finally, mitotic cells containing non-phosphorylatable and/or phosphorylation-insensitive alleles of initiation proteins do not require Cdc14p for DNA rereplication. These data...

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