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  • The EMBO Journal (2008) 27, 2250 - 2258
  • doi:10.1038/emboj.2008.135

Published online: 24 July 2008

Cryo-electron microscopy reveals a novel DNA-binding site on the MCM helicase

Alessandro Costa1,a, Gijs van Duinen1, Barbara Medagli1,2, James Chong3, Nozomi Sakakibara4, Zvi Kelman4, Satish K Nair5, Ardan Patwardhan1 and Silvia Onesti1,2

  1. Department of Life Sciences, Imperial College London, London, UK
  2. ELETTRA, Sincrotrone Trieste, Trieste, Italy
  3. Department of Biology, University of York, York, UK
  4. Center for Advanced Research in Biotechnology, University of Maryland, Rockville, MD, USA
  5. Department of Biochemistry, University of Illinois, Urbana, IL, USA

Correspondence to:

Silvia Onesti, Department of Life Sciences, Blackett Laboratory, Imperial College London, London SW7 2BZ, UK. Tel.: +44 207 594 7647; Fax: +44 207 594 5332; E-mail: s.onesti@imperial.ac.uk

aPresent address: Sir William Dunn School of Pathology, University of Oxford, Oxford, UK

Received 15 January 2008; Accepted 24 June 2008

The eukaryotic MCM2–7 complex is recruited at origins of replication during the G1 phase and acts as the main helicase at the replication fork during the S phase of the cell cycle. To characterize the interplay between the MCM helicase and DNA prior to the melting of the double helix, we determined the structure of an archaeal MCM orthologue bound to a 5.6-kb double-stranded DNA segment, using cryo-electron microscopy. DNA wraps around the N-terminal face of a single hexameric ring. This interaction requires a conformational change within the outer belt of the MCM N-terminal domain, exposing a previously unrecognized helix-turn-helix DNA-binding motif. Our findings provide novel insights into the role of the MCM complex during the initiation step of DNA replication.

  • Keywords:

    • AAA+ ATPase,
    • archaea,
    • DNA topology,
    • electron microscopy,
    • MCM2–7