A Multicopy Suppressor Gene of the <i>Saccharomyces cerevisiae</i> G ₁ Cell Cycle Mutant Gene <i>dbf4</i> Encodes a Protein Kinase and Is Identified as <i>CDC5</i>

We have isolated a multicopy suppressor of the temperature-sensitive growth phenotype of organisms carrying mutations of DBF4, a gene that is required for the initiation of chromosomal DNA replication in Saccharomyces cerevisiae and that interacts with the CDC7 protein kinase. Nucleotide sequence analysis of the suppressor gene, provisionally named MSD2, revealed an open reading frame encoding a protein with a calculated M(r) of 81,024, with amino acid sequence similarity to the catalytic domains of protein kinases. Both genetic linkage and complementation analyses indicated that MSD2 is identical to the cell division cycle gene CDC5. An activity that phosphorylated exogenously added casein was immunoprecipitated by antiserum against a TrpE-Cdc5 fusion protein from lysates of wild-type cells containing CDC5 on a multicopy…