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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.

Pubmed ID: 17018296

Authors

  • Sheu YJ
  • Stillman B

Journal

Molecular cell

Publication Data

October 6, 2006

Associated Grants

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

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