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. 2016 Dec;28(12):1852-1862.
doi: 10.1016/j.cellsig.2016.08.018. Epub 2016 Aug 31.

GINS Complex Protein Sld5 Recruits SIK1 to Activate MCM Helicase During DNA Replication

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GINS Complex Protein Sld5 Recruits SIK1 to Activate MCM Helicase During DNA Replication

Kiranmai Joshi et al. Cell Signal. .

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.

Keywords: Gins; MCM helicase; Replication; SIK1; Sld5.

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