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Joshi, Kiranmai and Shah, V.J. and Subba Reddy, Maddika (2016) GINS complex protein Sld5 recruits SIK1 to activate MCM helicase during DNA replication. Cellular Signalling, 28 (12). pp. 1852-1862. ISSN 0898-6568

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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.

Item Type: Article
Depositing User: Dr P Divakar
Date Deposited: 10 Sep 2016 17:03
Last Modified: 12 Sep 2016 04:15
URI: http://cdfd.sciencecentral.in/id/eprint/749

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