The structural basis for MCM2–7 helicase activation by GINS and Cdc45

Abstract

Two central steps for initiating eukaryotic DNA replication involve loading of the Mcm2–7 helicase onto double-stranded DNA and its activation by GINS–Cdc45. To better understand these events, we determined the structures of Mcm2–7 and the CMG complex by using single-particle electron microscopy. Mcm2–7 adopts two conformations—a lock-washer-shaped spiral state and a planar, gapped-ring form—in which Mcm2 and Mcm5 flank a breach in the helicase perimeter. GINS and Cdc45 bridge this gap, forming a topologically closed assembly with a large interior channel; nucleotide binding further seals off the discontinuity between Mcm2 and Mcm5, partitioning the channel into two smaller pores. Together, our data help explain how GINS and Cdc45 activate Mcm2–7, indicate that Mcm2–7 loading may be assisted by a natural predisposition of the hexamer to form open rings, and suggest a mechanism by which the CMG complex assists DNA strand separation.

DOI: 10.1038/nsmb.2004
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@article{Costa2011TheSB, title={The structural basis for MCM2–7 helicase activation by GINS and Cdc45}, author={Alessandro Costa and Ivar Ilves and Nele Tamberg and Tatjana Petojevic and Eva Nogales and Michael R Botchan and James M Berger}, journal={Nature Structural &Molecular Biology}, year={2011}, volume={18}, pages={471-477} }