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Assembly of the Cdc45-MCM2-7-GINS Complex, the Replication Helicase

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The Initiation of DNA Replication in Eukaryotes

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Abstract

In eukaryotes, a crucial step during the initiation of DNA replication is the timely formation and activation of the replicative DNA helicase composed of Cdc45, MCM2-7 and GINS (CMG). The dynamic and spatio-temporal events leading to the ordered and stepwise assembly of the CMG helicase are tightly regulated. Multiple assembly factors ensure in this way that replication occurs only once per cell cycle. The MCM2-7 helicase is loaded in an inactive form onto double-stranded DNA in the G1 phase of the cell cycle, whereas the fully reconstituted CMG complex is assembled and positioned onto single-stranded DNA during the S phase. Thus, DNA plays an important and active role in these events. In this chapter we summarize and discuss our current knowledge about the appropriate recruitment and assembly of the CMG complex into the active eukaryotic replicative DNA helicase, emphasizing the crucial role of DNA in this process. We finally outline how the number of active CMG complexes formed is restricted during unperturbed DNA synthesis.

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Acknowledgements

The Fritz Lipmann Institute (FLI) is member of the Science Association “Gottfried Wilhelm Leibniz” (WGL) and is financially supported by the Federal Government of Germany and the State of Thuringia. The authors are grateful to Frank Grosse for fruitful discussions and critical reading of the manuscript.

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  1. Research Group Biochemistry, Leibniz Institute on Aging-Fritz Lipmann Institute, Beutenbergstrasse 11, D-07745, Jena, Germany

    Helmut Pospiech & Anna Szambowska

  2. Faculty of Biochemistry and Molecular Medicine, University of Oulu, 5400, FI-90014, Oulu, Finland

    Helmut Pospiech

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  1. Helmut Pospiech
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Correspondence to Helmut Pospiech .

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  1. Florida State Univ. College of Medi, TALLAHASSEE, Florida, USA

    Daniel L. Kaplan

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Pospiech, H., Szambowska, A. (2016). Assembly of the Cdc45-MCM2-7-GINS Complex, the Replication Helicase. In: Kaplan, D. (eds) The Initiation of DNA Replication in Eukaryotes. Springer, Cham. https://doi.org/10.1007/978-3-319-24696-3_19

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