Mec1 is one of multiple kinases that prime the Mcm2-7 helicase for phosphorylation by Cdc7.

Activation of the eukaryotic replicative DNA helicase, the Mcm2-7 complex, requires phosphorylation by Cdc7/Dbf4 (Dbf4-dependent kinase or DDK), which, in turn, depends on prior phosphorylation of Mcm2-7 by an unknown kinase (or kinases). We identified DDK phosphorylation sites on Mcm4 and Mcm6 and found that phosphorylation of either subunit suffices ...
for cell proliferation. Importantly, prior phosphorylation of either S/T-P or S/T-Q motifs on these subunits is required for DDK phosphorylation of Mcm2-7 and for normal S phase passage. Phosphomimetic mutations of DDK target sites bypass both DDK function and mutation of the priming phosphorylation sites. Mrc1 facilitates Mec1 phosphorylation of the S/T-Q motifs of chromatin-bound Mcm2-7 during S phase to activate replication. Genetic interactions between priming site mutations and MRC1 or TOF1 deletion support a role for these modifications in replication fork stability. These findings identify regulatory mechanisms that modulate origin firing and replication fork assembly during cell cycle progression.
Mesh Terms:
Amino Acid Sequence, Amino Acids, Cell Cycle, Cell Cycle Proteins, Chromatin, Chromosomal Proteins, Non-Histone, DNA-Binding Proteins, Intracellular Signaling Peptides and Proteins, Models, Biological, Molecular Sequence Data, Mutation, Nuclear Proteins, Phenotype, Phosphorylation, Protein-Serine-Threonine Kinases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
Mol. Cell
Date: Nov. 12, 2010
Download Curated Data For This Publication
111272
Switch View:
  • Interactions 2
  • PTM Genes 5