, Volume 124, Issue 1, pp 13–26 | Cite as

Switch on the engine: how the eukaryotic replicative helicase MCM2–7 becomes activated

  • Silvia Tognetti
  • Alberto Riera
  • Christian SpeckEmail author


A crucial step during eukaryotic initiation of DNA replication is the correct loading and activation of the replicative DNA helicase, which ensures that each replication origin fires only once. Unregulated DNA helicase loading and activation, as it occurs in cancer, can cause severe DNA damage and genomic instability. The essential mini-chromosome maintenance proteins 2–7 (MCM2–7) represent the core of the eukaryotic replicative helicase that is loaded at DNA replication origins during G1-phase of the cell cycle. The MCM2–7 helicase activity, however, is only triggered during S-phase once the holo-helicase Cdc45-MCM2–7-GINS (CMG) has been formed. A large number of factors and several kinases interact and contribute to CMG formation and helicase activation, though the exact mechanisms remain unclear. Crucially, upon DNA damage, this reaction is temporarily halted to ensure genome integrity. Here, we review the current understanding of helicase activation; we focus on protein interactions during CMG formation, discuss structural changes during helicase activation, and outline similarities and differences of the prokaryotic and eukaryotic helicase activation process.


Replication Fork Replication Origin Helicase Activation BRCT Domain ssDNA Binding 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We would like to thank A. Okorokov, C. Herrera, Y. Javadi and F. Pisani for comments on the manuscript, and Imperial College and the MRC for funding.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Silvia Tognetti
    • 1
  • Alberto Riera
    • 1
  • Christian Speck
    • 1
    Email author
  1. 1.DNA Replication Group, Institute of Clinical ScienceImperial CollegeLondonUK

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