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Organization of the archaeal MCM complex on DNA and implications for the helicase mechanism

Nature Structural & Molecular Biology volume 12, pages 756–762 (2005)Cite this article

Abstract

The homomultimeric archaeal mini-chromosome maintenance (MCM) complex serves as a simple model for the analogous heterohexameric eukaryotic complex. Here we investigate the organization and orientation of the MCM complex of the hyperthermophilic archaeon Sulfolobus solfataricus (Sso) on model DNA substrates. Sso MCM binds as a hexamer and slides on the end of a 3′-extended single-stranded DNA tail of a Y-shaped substrate; binding is oriented so that the motor domain of the protein faces duplex DNA. Two candidate β-hairpin motifs within the MCM monomer have partially redundant roles in DNA binding. Notably, however, conserved basic residues within these motifs have nonequivalent roles in the helicase activity of MCM. On the basis of these findings, we propose a model for the mechanism of the helicase activity of MCM and note parallels with SV40 T antigen.

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Figure 1: Two candidate β-hairpins in Sso MCM.
Figure 2: Biochemical characterization of Sso MCM.
Figure 3: Architecture of MCM and orientation on DNA.
Figure 4: Loading of Sso MCM onto DNA.
Figure 5: Cutaway model of MCM binding to DNA.

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Acknowledgements

Work in the laboratory of S.D.B. is supported by the Medical Research Council. A.T.M. was additionally funded by Cambridge Clinical School. M.A.T. would also like to thank the Royal Society for generous funding. We thank N. Thorne for help with statistical distribution corrections and Z. Kelman for stimulating discussions.

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  1. Adam T McGeoch and Michael A Trakselis: These authors contributed equally toward this work.

Authors and Affiliations

  1. MRC Cancer Cell Unit, Hutchison MRC Research Centre, Hills Road, Cambridge, CB2 2XZ, UK

    Adam T McGeoch, Michael A Trakselis, Ronald A Laskey & Stephen D Bell

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Correspondence to Stephen D Bell.

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McGeoch, A., Trakselis, M., Laskey, R. et al. Organization of the archaeal MCM complex on DNA and implications for the helicase mechanism. Nat Struct Mol Biol 12, 756–762 (2005). https://doi.org/10.1038/nsmb974

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