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DESCRIPTION: ORC, the origin recognition complex, is a multi-subunit protein complex that is composed of 6 different proteins ranging in molecular weight from 50 to 120 kDa. The complex was originally identified in S. cerevisiae and is essential for the initiation of DNA replication. The proteins bind to a specific recognition sequence in the origin region and remain bound to the DNA throughout the cell cycle. The second largest of the proteins, the 71 kDa Orc2p, is encoded by ORC2. ORC2, also called RRR1 or SIR5, is an essential gene in S. cerevisiae and is required for both replication and transcriptional silencing. ORC is present at little more than one complete complex per replication origin and binds at origins immediately after initiation in the previous cell cycle. Assembly of additional complexes occurs in multiple stages during the cell cycle and includes a pre-replicative complex (pre-RC) as well as other proteins. Orc2p, along with Orc5p, forms a complex with Cdc6p, a protein required for initiation of DNA replication. Since ORC and Cdc6p bind as a complex at individual DNA replication origins, ORC and Cdc6p may cooperate to determine the frequency of initiation of replication and also repress transcription of specific genes. Although the origin of DNA replication has been difficult to demonstrate in other eukaryotic species, the ORC function has been conserved through eukaryotes with orthologs of ORC2 having been identified in other eukaryotes including humans, mice, C. elegans, Drosophila, Xenopus, and various yeast and plant species.
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