Symmetrical CMG Activation Unveiled by Cryo-EM in Yeast Replication Initiation
Using a purified yeast reconstitution and cryo-EM, researchers captured a pre-initiation complex with two symmetric CMG helicases assembling from firing factors, revealing stepwise MCM remodeling and how ATP promotes ejection of assembly factors to mature into active CMG–Pol ε complexes. They show Sld2 enhances GINS delivery and lagging-strand ejection after CMGE formation, while Dpb11 coordinates two MCMs by engaging Mcm7 and GINS across the hexamers, enabling bidirectional origin firing. The work ties Sld2’s function to RECQL4 in metazoans and suggests a conserved mechanism linking double-CMG separation, fork establishment, and factor eviction downstream of CMGE activation.