Pre-replication complex

A pre-replication complex (pre-RC) is a protein complex that forms at the origin of replication during the initiation step of DNA replication. Formation of the pre-RC is required for DNA replication to occur. Complete and faithful replication of the genome ensures that each daughter cell will carry the same genetic information as the parent cell. Accordingly, formation of the pre-RC is a very important part of the cell cycle. As organisms evolved and became increasingly more complex, so did their pre-RCs. The following is a summary of the components of the pre-RC amongst the different domains of life. In bacteria, the main component of the pre-RC is DnaA. The pre-RC is complete when DnaA occupies all of its binding sites within the bacterial origin of replication (oriC). The archaeal pre-RC is very different from the bacterial pre-RC and can serve as a simplified model of the eukaryotic pre-RC. It is composed of a single origin recognition complex (ORC) protein, Cdc6/ORC1, and a homohexamer of the minichromosome maintenance (MCM) protein. Sulfolobus islandicus also uses a Cdt1 homologue to recognize one of its replication origins. The eukaryotic pre-RC is the most complex and highly regulated pre-RC. In most eukaryotes it is composed of six ORC proteins (ORC1-6), Cdc6, Cdt1, and a heterohexamer of the six MCM proteins (MCM2-7). The MCM heterohexamer arguably arose via MCM gene duplication events and subsequent divergent evolution. The pre-RC of Schizosaccharomyces pombe (S. pombe) is notably different from that of other eukaryotes; Cdc6 is replaced by the homologous Cdc18 protein. Sap1 is also included in the S. pombe pre-RC because it is required for Cdc18 binding. The pre-RC of Xenopus laevis (X. laevis) also has an additional protein, MCM9, which helps load the MCM heterohexamer onto the origin of replication. The structure of the ORC, MCM, as well as the intermediate ORC-Cdc6-Cdt1-Mcm2-7 (OCCM) complex has been resolved. Recognition of the origin of replication is a critical first step in the formation of the pre-RC.