Cdc7-Dbf4 phosphorylates MCM proteins via a docking site-mediated mechanism to promote S phase progression.

Origins of DNA replication are licensed in G1 by recruiting the minichromosome maintenance (MCM) proteins to form a prereplicative complex (pre-RC). Prior to initiation of DNA synthesis from each origin, a preinitiation complex (pre-IC) containing Cdc45 and other proteins is formed. We report that Cdc7-Dbf4 protein kinase (DDK) promotes assembly ...
of a stable Cdc45-MCM complex exclusively on chromatin in S phase. In this complex, Mcm4 is hyperphosphorylated. Studies in vitro using purified DDK and Mcm4 demonstrate that hyperphosphorylation occurs at the Mcm4 N terminus. However, the DDK substrate specificity is conferred by an adjacent DDK-docking domain (DDD), sufficient for facilitating efficient phosphorylation of artificial phosphoacceptors in cis. Genetic evidence suggests that phosphorylation of Mcm4 by DDK is important for timely S phase progression and for cell viability upon overproduction of Cdc45. We suggest that DDK docks on and phosphorylates MCM proteins at licensed origins to promote proper assembly of pre-IC.
Mesh Terms:
Amino Acid Motifs, Apoenzymes, Binding Sites, Cell Cycle Proteins, Chromatin, Conserved Sequence, DNA Replication, DNA-Binding Proteins, Models, Biological, Molecular Sequence Data, Nuclear Proteins, Phosphorylation, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, S Phase, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Sequence Alignment
Mol. Cell
Date: Oct. 06, 2006
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