Like any monumental task, configuring chromosomes for replication requires a certain amount of preparation. For eukaryotic cells, this preparation begins early in G 1 , when DNA is made replication-ready by the recruitment of proteins to the sites along each chromosome where replication will begin. These nucleotide sequences, called origins of replication, serve as landing pads for the proteins and protein complexes that control and carry out DNA synthesis.

One of these protein complexes, called the origin recognition complex (ORC), remains perched on the replication origins throughout the cell cycle. To prepare the DNA for replication, the ORC recruits a protein called Cdc6, whose concentration rises early in G 1 . Together, these proteins load the DNA helicases that will ultimately open up the double helix at the origin of replication. Once this prereplicative complex is in place, the replication origin is loaded and ready to “fire.”