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 from G1 to S phase and later required to prevent the re-initiation of DNA replication during G2. 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 initiation. Fission yeast Orp2 is required for DNA replication and interacts with the rate-limiting replication activator Cdc18. Cells lacking Orp2 undergo aberrant mitosis, indicating that Orp2 is involved in generating a checkpoint signal. These findings suggest that ORC functions are conserved among eukaryotes and provide evidence that Cdc2 controls DNA replication initiation by acting directly at chromosomal origins.
Leatherwood
J
J
Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92037, USA.
Lopez-Girona
A
A
Russell
P
P
D000595:Amino Acid Sequence; D001483:Base Sequence; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D017931:DNA Primers; D004261:DNA Replication / Q000502:physiology; D004271:DNA, Fungal / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis; D008969:Molecular Sequence Data; D009154:Mutation; D051738:Origin Recognition Complex; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D018741:Replication Origin; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins
D018797:Cell Cycle Proteins; D017931:DNA Primers; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C497215:ORC2 protein, S cerevisiae; D051738:Origin Recognition Complex; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C082462:cdc18 protein, S pombe; C097704:orc2 protein, S pombe; D016203:CDC2 Protein Kinase