INTERACTION OF CDC2 AND CDC18 WITH A FISSION YEAST ORC2-LIKE PROTEIN

IN fission yeast, Cdc2 kinase has both positive and negative roles in regulating DNA replication, being first necessary for the transition f rom G(1) to S phase and later required to prevent the re-initiation of DNA replication during G(2)(1-3). We report here that Cdc2 interacts with Orp2, a protein similar to the Orc2 replication factor subunit of Saccharomyces cerevisiae origin recognition complex (ORC). ORC binds chromosomal origins and is essential for chromosomal replication initi ation(4-6). Fission yeast Orp2 is required for DNA replication and int eracts with the rate-limiting replication activator Cdc18. Cells lacki ng Orp2 undergo aberrant mitosis, indicating that Orp2 is involved in generating a checkpoint signal, These findings suggest that ORC functi ons are conserved among eukaryotes and provide evidence that Cdc2 cont rols DNA replication initiation by acting directly at chromosomal orig ins.