Shah, Varun Jayeshkumar (2016) GINS complex protein Sld5 recruits SIK1 to activate MCMhelicase during DNA replication. Cellular Signalling, 28. pp. 1852-1862. ISSN 0898-6568

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Abstract

In eukaryotes, proper loading and activation ofMCM helicase at chromosomal origins plays a central role in DNA replication. Activation of MCMhelicase requires its associationwith CDC45-GINS complex, but the mechanismof howthis complex activatesMCMhelicase 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 MCMhelicase 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 phosphorylatesMCM2 at five conserved residues at its N-terminus, which is essential for the activation ofMCM helicase. Collectively, our results suggest SIK1 as a novel integral component of CMG replicative helicase during eukaryotic DNA replication

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