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The molecular interactions involved in DNA replication insure coordinated replication of the entire genome once and only once per cell cycle. The molecular pathways involved in replication can be separated into 3 clear components: licensing, initiation, and regulatory interactions. During licensing, which occurs in late mitosis and early G1, post-mitotic unreplicated chromatin binds several protein complexes. Initiation of DNA replication, occurring throughout S-phase, requires binding of additional factors that recruit the components of the replication machinery. After replication, the protein complexes that form the licensing factor leave the DNA, and the DNA is not a substrate for further initiations. Regulatory interactions occur on licensed or unlicensed chromatin as a response to environmental conditions that determine whether cells proceed or halt their progression through the cell cycle. These interactions, primarily through modifications of the phosphorylation status of proteins involved in licensing and initiation, determine whether replication will occur on a specific template during a specific time of the cell cycle.

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