Cdc7p is a protein kinase that is required for G 1 ͞S transition and initiation of DNA replication in Saccharomyces cerevisiae. The mechanisms whereby Cdc7p and its substrates exerts their effects are unknown. We report here the characterization in S. cerevisiae of a recessive mutation in a member of the MCM family, MCM5͞CDC46, which bypasses the requirement for Cdc7p and its interacting factor Dbf4p. Because the MCM family of evolutionarily conserved proteins have been implicated in restricting DNA replication to once per cell cycle, our studies suggest that Cdc7p is required late in G 1 because in its absence the Mcm5p͞Cdc46p blocks the initiation of DNA replication. Moreover, Mcm5p͞Cdc46p may have both positive and negative effects on the ability of cell to initiate replication.
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