Replication

DNA replication must be tightly coordinated with cell division, so that extra copies of chromosomes are not created and each daughter cell receives exactly the right number of each chromosome. DNA replication is regulated by DNA replication proteins.

controlling the assembly of complexes at replication origins. In bacteria, the accumulation of the initiator protein, dnaA, seems to be an important factor in determining when replication begins.

In eukaryotes, DNA replication and cell division are separated by two "gap" cell cycle phases (G₁ and G₂), during which neither DNA replication nor nuclear division occurs. DNA replication occurs during the S (or synthesis) phase, but ORC is thought to bind replication origins throughout the cell cycle. During the G₁ phase of the cell cycle, ORC helps to assemble other replication initiation factors at replication origins to make so-called pre-replicative-complexes (pre-RCs) that are competent to initiate replication during S phase. These other initiation factors include a protein called Cdc6 and a family of six related MCM ("mini-chromosome maintenance") proteins. The functions of these proteins are not yet known; however, the MCM proteins are currently the best candidate for the eukaryotic replicative helicase, and Cdc6 is necessary for MCM proteins to bind DNA. DNA polymerase also assembles on origins during this time.

Replication initiation is actually triggered at the beginning of S phase by the phosphorylation (addition of a phosphate group to) of one or more proteins in the pre-RC. The enzymes that phosphorylate proteins in the pre-RC are called protein kinases. Once they become active, they not only trigger replication initiation, but they also prevent the assembly of new pre-RCs. Therefore, replication cannot begin again until cells have completed cell division and entered G₁ phase again.