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The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).

Two states at the origin of replication

In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication. During the progression of the cell cycle, the origins of replication exist in two states. The first state exists in the G1-phase when a multiprotein complex called the pre-replicative complex (pre-RC) assembles on the origin. The second state exists from the initiation of the S-phase to the end of the M-phase when a complex with fewer components called the post-replicative complex (post-RC) remains on the origin DNA.

Cdk activity controls each round of DNA replication

At the end of the M-phase, cyclin-dependent kinase (Cdk) activity is low within the cells, which permits the pre-RC assembly, resulting in a replication-competent state. During the G1—S phase transition, Cdk activity increases, triggering DNA replication initiation. The increased Cdk activity also causes the disassembly of the pre-RC complex, converting the origin to a post-RC state. Throughout the S-phase and the remainder of the cell cycle, persistent high Cdk activity prevents the re-assembly of pre-RC until the end of mitosis when the Cdk activity again reduces. This control mechanism inhibits re-replication.

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