Origin of replication

Cells have control of where DNA replication is initiated as well how many times it is initiated. ORC (origin replication complex) initially binds to the origin of replication on the DNA and causes replication to go off in two directions. Once two replication complexes meet up in the middle, they finish their replication and dissociate. For our purposes we will assume that ORC is bound to DNA all the time. ORC binds, recruits Cdc6 (an ATPase), which then recruits other complexes, including helicase(MCM). Cdt1 brings helicase to the ORC. In S-phase, CDK phosphorylates the ORC, cdc6 and helicase. This effectively prevents the formation of the preRC (pre replication complex). This ensures that the DNA is only replicated once during one round of the cell cycle. PreRC assembly is known as origin licensing. When Rb lets go of E2F, the preRC is assembled. Phosphorylation of ORC stop cdc6 from binding, phosphorylation of cdc6 degrades it, phosphorylation of helicase cause exporitin to bind it and take it out of the nucleus. CDK is responsible for replication initiation as well as ensuring replication only happens once.