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

Molecular cell | Oct 6, 2006

http://www.ncbi.nlm.nih.gov/pubmed/17018296

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.

Pubmed ID: 17018296 RIS Download

Mesh terms: Amino Acid Motifs | Apoenzymes | Binding Sites | Cell Cycle Proteins | Chromatin | Conserved Sequence | DNA Replication | DNA-Binding Proteins | Minichromosome Maintenance Complex Component 4 | Models, Biological | Molecular Sequence Data | Nuclear Proteins | Phosphorylation | Protein Structure, Tertiary | Protein-Serine-Threonine Kinases | S Phase | Saccharomyces cerevisiae | Saccharomyces cerevisiae Proteins | Sequence Alignment

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Associated grants

  • Agency: NIGMS NIH HHS, Id: GM 45436
  • Agency: NIGMS NIH HHS, Id: R01 GM045436
  • Agency: NIGMS NIH HHS, Id: R01 GM045436-18

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