Helicase loading: how to build a MCM2-7 double-hexamer.

•The replicative helicase MCM2-7 is loaded by ORC, Cdc6 and Cdt1 at replication origins into pre-replicative complexes (pre-RC).•During helicase loading two MCM2-7 hexamers assemble into a double-hexamer bound around double-stranded DNA.•MCM2-7 double-hexamer formation is a multi-step reaction that requires ATP hydrolysis.•CDK affects the stability of the ORC/Cdc6/MCM2-7 pre-RC intermediate for regulated helicase loading and genome stability.•Inhibition of helicase loading affects cancer cell viability and could be of therapeutic value.