Functionally homologous DNA replication genes in fission and budding yeast

The cdc18(+) gene of the fission yeast Schizosaccharomyces pombe is involve d in the initiation of DNA replication as well as in coupling the S phase t o mitosis, In this work, we show that the Saccharomyces cerevisiae CDC6 gen e complements cdc18-K46 ts and cdc18 deletion mutant S, pombe strains. The budding yeast gene suppresses both the initiation and the checkpoint defect s associated with the lack of cdc18(+), The Cdc6 protein interacts in vivo with Cdc2 kinase complexes. Interestingly, Cdc6 is an in vitro substrate fo r Cdc13/Cdc2 and Cig1/Cdc2, but not for Cig2/Cdc2-associated kinases, Overe xpression of Cdc6 in fission yeast induces multiple rounds of S-phase in th e absence of mitosis and cell division. This CDC6-dependent continuous DNA synthesis phenotype is independent of the presence of a functional cdc18(+) gene product and, significantly, requires only Cig2/Cdc2-associated kinase activity. Finally, these S, pombe over-replicating cells do not require an y protein synthesis other than that of Cdc6. Our data strongly suggest that CDC6 and cdc18(+) are functional homologues and also support the idea that controls restricting genome duplication in fission and diverge budding yea st.