GINS complex protein Sld5 recruits SIK1 to activate MCM helicase during DNA replication.
In eukaryotes, proper loading and activation of MCM helicase at chromosomal origins plays a central role in DNA replication. Activation of MCM helicase requires its association with CDC45-GINS complex, but the mechanism of how this complex activates MCM helicase is poorly understood. Here we identified SIK1 (salt-inducible kinase 1), an ... AMPK related protein kinase, as a molecular link that connects GINS complex with MCM helicase activity. We demonstrated that Sld5 a component of GINS complex interacts with SIK1 and recruits it to the sites of DNA replication at the onset of S phase. Depletion of SIK1 leads to defective DNA replication. Further, we showed that SIK1 phosphorylates MCM2 at five conserved residues at its N-terminus, which is essential for the activation of MCM helicase. Collectively, our results suggest SIK1 as a novel integral component of CMG replicative helicase during eukaryotic DNA replication.
Mesh Terms:
Amino Acid Sequence, Chromosomal Proteins, Non-Histone, DNA Replication, G1 Phase, HeLa Cells, Humans, Minichromosome Maintenance Complex Component 2, Models, Biological, Multiprotein Complexes, Phosphorylation, Protein-Serine-Threonine Kinases, S Phase
Amino Acid Sequence, Chromosomal Proteins, Non-Histone, DNA Replication, G1 Phase, HeLa Cells, Humans, Minichromosome Maintenance Complex Component 2, Models, Biological, Multiprotein Complexes, Phosphorylation, Protein-Serine-Threonine Kinases, S Phase
Cell. Signal.
Date: Dec. 01, 2015
PubMed ID: 27592030
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