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Incorporation into the prereplicative complex activates the Mcm2-7 helicase for Cdc7-Dbf4 phosphorylation.

Genes & development | Mar 1, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19270162

The essential S-phase kinase Cdc7-Dbf4 acts at eukaryotic origins of replication to trigger a cascade of protein associations that activate the Mcm2-7 replicative helicase. Also known as Dbf4-dependent kinase (DDK), this kinase preferentially targets chromatin-associated Mcm2-7 complexes that are assembled on the DNA during prereplicative complex (pre-RC) formation. Here we address the mechanisms that control the specificity of DDK action. We show that incorporation of Mcm2-7 into the pre-RC increased the level and changes the specificity of DDK phosphorylation of this complex. In the context of the pre-RC, DDK preferentially targets a conformationally distinct subpopulation of Mcm2-7 complexes that is tightly linked to the origin DNA. This targeting requires DDK to tightly associate with Mcm2-7 complexes in a Dbf4-dependent manner. Importantly, we find that DDK association with and phosphorylation of origin-linked Mcm2-7 complexes require prior phosphorylation of the pre-RC. Our findings provide insights into the mechanisms that ensure that DDK action is spatially and temporally restricted to the origin-bound Mcm2-7 complexes that will drive replication fork movement during S phase and suggest new mechanisms to regulate origin activity.

Pubmed ID: 19270162 RIS Download

Mesh terms: Cell Cycle Proteins | Chromosomal Proteins, Non-Histone | DNA Replication | DNA-Binding Proteins | Fungal Proteins | Minichromosome Maintenance Complex Component 7 | Nuclear Proteins | Phosphorylation | Protein Binding | Protein-Serine-Threonine Kinases | Saccharomyces cerevisiae | Saccharomyces cerevisiae Proteins

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Associated grants

  • Agency: NIGMS NIH HHS, Id: GM007287
  • Agency: NIGMS NIH HHS, Id: GM52339
  • Agency: NIGMS NIH HHS, Id: R01 GM052339
  • Agency: Howard Hughes Medical Institute, Id:

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