Initiation of DNA Replication
DNA replication is initiated by a multiprotein complex referred to as the pre-replicative complex (preRC). Assembly of the preRC occurs in a highly ordered, cell cycle-dependent manner at established loci within the genome which are designated "replication origins". As cells enter G1 from mitosis:
1) a six-subunit origin recognition complex (ORC) binds replication origins throughout the genome
2) Cdc6 and Cdt1 are independently recruited to the ORC
3) These factors recruit the hexameric MCM complex (MCMs 2-7) which loads onto the replication origin to function as the replicative helicase.
As cells progress from G1 into early S, the preRC recruits functional replication complexes that contain DNA polymerases and associated "processivity" factors (ex. proliferatin cell nuclear antigen a.k.a. PCNA). Following firing of the origin, the S- and M- phase CDKs then phosphorylate Cdc6 to mark it for ubiquitination and degredation, thus dissociating the preRC to prevent endoreduplication.
1) a six-subunit origin recognition complex (ORC) binds replication origins throughout the genome
2) Cdc6 and Cdt1 are independently recruited to the ORC
3) These factors recruit the hexameric MCM complex (MCMs 2-7) which loads onto the replication origin to function as the replicative helicase.
As cells progress from G1 into early S, the preRC recruits functional replication complexes that contain DNA polymerases and associated "processivity" factors (ex. proliferatin cell nuclear antigen a.k.a. PCNA). Following firing of the origin, the S- and M- phase CDKs then phosphorylate Cdc6 to mark it for ubiquitination and degredation, thus dissociating the preRC to prevent endoreduplication.