GINS complex protein Sld5 recruits SIK1 to activate MCMhelicase during DNA replication

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

Item Type: Article
Uncontrolled Keywords: Gins; Sld5; Replication; SIK1; MCM helicase
Subjects: Research > Research Center - Health Sciences
Depositing User: KMC Library
Date Deposited: 06 Aug 2019 03:51
Last Modified: 06 Aug 2019 03:51
URI: http://eprints.manipal.edu/id/eprint/154241

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