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5.05: DNA Replication

Last updated: Mar 30, 2026

Image unavailable: Diagram of DNA replication fork, showing template strands, leading and lagging strands, DNA polymerase, DNA ligase, and Okazaki fragments. Arrows indicate direction of replication.
Figure 5.5.3: Control of Replication

With their multiple origins, how does the eukaryotic cell know which origins have been already replicated and which still await replication?

An observation: When a cell in G2 of the cell cycle is fused with a cell in S phase, the DNA of the G2 nucleus does not begin replicating again even though replication is proceeding normally in the S-phase nucleus. Not until mitosis is completed, can freshly-synthesized DNA be replicated again.

Two control mechanisms have been identified — one positive and one negative. This redundancy probably reflects the crucial importance of precise replication to the integrity of the genome.

Licensing: positive control of replication

In order to be replicated, each origin of replication must be bound by:

  • an Origin Recognition Complex of proteins (ORC). These remain on the DNA throughout the process.
  • Accessory proteins called licensing factors. These accumulate in the nucleus during G1 of the cell cycle. They include:
    • Cdc-6 and Cdt-1, which bind to the ORC and are essential for coating the DNA with
    • MCM proteins. Only DNA coated with MCM proteins (there are 6 of them) can be replicated.

Once replication begins in S phase,

  • Cdc-6 and Cdt-1 leave the ORCs (the latter by ubiquination and destruction in proteasomes).
  • The MCM proteins leave in front of the advancing replication fork.