期刊
CELLULAR SIGNALLING
卷 28, 期 12, 页码 1852-1862出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2016.08.018
关键词
Gins; Sld5; Replication; SIK1; MCM helicase
类别
资金
- Council of Scientific and Industrial Research, India [37(1466)/11/EMR-II]
- CDFD core funds
- Wellcome Trust/DBT India Alliance [500230/Z/11/Z]
- Department of Biotechnology (DBT), India
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. (C) 2016 Elsevier Inc. All rights reserved.
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