Cryo-EM structure of a licensed DNA replication origin

Ferdos Abid Ali, Max E. Douglas, Julia Locke, Valerie E. Pye, Andrea Nans, John F. X. Diffley and Alessandro Costa ()
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Ferdos Abid Ali: The Francis Crick Institute
Max E. Douglas: The Francis Crick Institute
Julia Locke: The Francis Crick Institute
Valerie E. Pye: The Francis Crick Institute
Andrea Nans: The Francis Crick Institute
John F. X. Diffley: The Francis Crick Institute
Alessandro Costa: The Francis Crick Institute

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: Abstract Eukaryotic origins of replication are licensed upon loading of the MCM helicase motor onto DNA. ATP hydrolysis by MCM is required for loading and the post-catalytic MCM is an inactive double hexamer that encircles duplex DNA. Origin firing depends on MCM engagement of Cdc45 and GINS to form the CMG holo-helicase. CMG assembly requires several steps including MCM phosphorylation by DDK. To understand origin activation, here we have determined the cryo-EM structures of DNA-bound MCM, either unmodified or phosphorylated, and visualize a phospho-dependent MCM element likely important for Cdc45 recruitment. MCM pore loops touch both the Watson and Crick strands, constraining duplex DNA in a bent configuration. By comparing our new MCM–DNA structure with the structure of CMG–DNA, we suggest how the conformational transition from the loaded, post-catalytic MCM to CMG might promote DNA untwisting and melting at the onset of replication.

Date: 2017
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DOI: 10.1038/s41467-017-02389-0

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