Conducting the finale of DNA replication.

Anomalies in dismantling the machinery of DNA replication can compromise genome integrity and contribute to tumorigenesis and aging. In this issue of , Dewar and colleagues (pp. 275-290) identified an E3 ubiquitin ligase, CUL2, that modifies a subunit of the replicative CMG (Cdc45, minichromosome maintenance [MCM] subunits 2-7, and the GINS complex) helicase and triggers disassembly of the replication machinery. Their study offers critical insight into the mechanism of DNA replication termination while at the same time raising important questions for future research.