Structure of the pre-initiation complex explains CMGE biogenesis - PubMed
3 hours ago
- #DNA replication
- #pre-initiation complex
- #CMGE biogenesis
- When cells enter S phase, bidirectional DNA replication begins with the regulated recruitment of Cdc45, GINS, and Pol ε activators to an MCM double hexamer bound to duplex DNA.
- This assembly forms two CMGE helicases that establish divergent replication forks as they separate.
- The study reconstituted the yeast pre-initiation complex and used cryo-EM to capture firing factors assembling two symmetrical CMGEs.
- The findings show how stepwise complex formation remodels MCM for DNA opening and how ATP promotes firing-factor ejection and CMGE maturation.
- Sld2 aids in recruiting GINS to MCM, helps separate the CMGE dimer, and is essential for ejecting the lagging strand from MCM.
- The insights extend to the metazoan orthologue RECQL4, suggesting a conserved eukaryotic mechanism for replication fork establishment.