Orp1, a member of the Cdc18/Cdc6 family of S-phase regulators, is homologous to a component of the origin recognition complex

cdc18⁺ of Schizosaccharomyces pombe a periodically expressed gene that is required for entry into S phase and for the coordination of S phase with mitosis. cde18⁺ is related to the Saccharomyces cerevisiae gene CDC6, which has also been implicated in the control of DNA replication. We have identified a new Sch. pombe gene, orp1⁺, that encodes an 80-kDa protein with amino acid sequence motifs conserved in the Cdc18 and Cdc6 proteins. Genetic analysis indicates that orp1⁺ is essential for viability. Germinating spores lacking the orp1⁺ gene are capable of undergoing one or more rounds of DNA replication but fail to progress further, arresting as long cells with a variety of deranged nuclear structures. Unlike cdc18⁺, orp1⁺ is expressed constitutively during the cell cycle. cdc18⁺, CDC6, and orp1⁺ belong to a family of related genes that also includes the gene ORC1, which encodes a subunit of the origin recognition complex (ORC) of S. cerevisiae. The products of this gene family share a 250-amino acid domain that is highly conserved in evolution and contains several characteristic motifs, including a consensus purine nucleotide-binding motif. Among the members of this gene family, orp1⁺ is most closely related to S. cerevisiae ORC1. Thus, the protein encoded by orp1⁺ may represent a component of an Sch. pombe ORC. The orp1⁺ gene is also closely related to an uncharacterized putative human homologue. It is likely that the members of the cdc18/CDC6 family play key roles in the regulation of DNA replication during the cell cycle of diverse species from archaebacteria to man.