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GINS complex protein Sld5 recruits SIK1 to activate MCM helicase during DNA replication.

Cellular signalling (2016-09-07)
Kiranmai Joshi, Varun Jayeshkumar Shah, Subbareddy Maddika
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Influenza Hemagglutinin (HA) Peptide, ≥97% (HPLC)
Sigma-Aldrich
MISSION® esiRNA, targeting human SIK1, CH507-42P11.8

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