ORC (Origin Replication Complex)

The ORC (Origin Replication Complex) is a proteic binding complex, made up of 6 subunits (ORC p1, ORC p2, ORC p3, ORC p4, ORC p5, ORC p6) that has a binding specificity to DNA, more specifically to the origins of replication, in the presence of ATP, in the genomes of the eukaryotes. Theoretically this binding complex’s function is the initiation and/or regulation of the DNA replication in eukaryotes.

For example, in the origin of replication ARS (Autonomously Replicating Sequence) of Saccharomyces cerevisiae, there are, as in the origin of replication of Escherichia coli, segments with different functional roles, and in both cases, these “subdomains” have similar sequences. 4 of these subdomains in Saccharomyces cerevisiae are known, and two of those – the subdomains A1 and B1 – constitute the origin recognition sequence, a segment of 40 bp that is the site where the ORC is going to bind to. The ORCs have been described as versions of the initiation proteins present in prokaryotes and viruses, such as the DnaA protein of Escherichia coli, which possess an initiation function in DNA replication by opening the double helix, but this interpretation is probably not entirely correct, because ORCs appear to remain attached to the yeast’s origins of replication throughout the cell cycle. 

This indicates that rather than being genuine initiation proteins, ORCs are more likely involved in the regulation of the genome’s replication, acting as mediators between the origins of replication and the regulating signals that coordinate the initiation of the replication of the DNA, with the cell cycle. More specifically, the ORC bound to the origins of replication act as the foundation for the assembly of the pre-replication complex (pre-RC), which is a proteic complex essential for the initiation of the replication, in other words, the pre-RCs act as licensing factor of the chromosomes. That’s why ORCs do not work directly in DNA replication initiation but indirectly instead.  In addition to this, the ORC is target of protein kinases which will phosphorylate some of it’s subunits in order to regulate DNA replication initiation and to block the reinitiation of the G2/M phases.

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