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GINS maintains association of Cdc45 with MCM in replisome progression complexes at eukaryotic DNA replication forks

Nature Cell Biology volume 8, pages 358–366 (2006)Cite this article

An Erratum to this article was published on 12 March 2006

Abstract

The components of the replisome that preserve genomic stability by controlling the progression of eukaryotic DNA replication forks are poorly understood. Here, we show that the GINS (go ichi ni san) complex allows the MCM (minichromosome maintenance) helicase to interact with key regulatory proteins in large replisome progression complexes (RPCs) that are assembled during initiation and disassembled at the end of S phase. RPC components include the essential initiation and elongation factor, Cdc45, the checkpoint mediator Mrc1, the Tof1–Csm3 complex that allows replication forks to pause at protein–DNA barriers, the histone chaperone FACT (facilitates chromatin transcription) and Ctf4, which helps to establish sister chromatid cohesion. RPCs also interact with Mcm10 and topoisomerase I. During initiation, GINS is essential for a specific subset of RPC proteins to interact with MCM. GINS is also important for the normal progression of DNA replication forks, and we show that it is required after initiation to maintain the association between MCM and Cdc45 within RPCs.

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Figure 6: GINS is required for specific RPC components to associate with MCM and thus with origins.
Figure 1: GINS–MCM complexes contain many regulators of replication fork progression.
Figure 2: Stable interaction of GINS with other regulators of replication fork progression is not mediated by DNA.
Figure 3: GINS and MCM form large RPCs that also contain other regulators of replication fork progression.
Figure 4: RPCs are only present during S phase.
Figure 5: RPC formation requires loading of MCM at origins.
Figure 7: GINS is required to maintain the interaction between MCM and specific RPC components after initiation.

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Acknowledgements

We thank K. Chiang for help with yeast strain construction, E. Schiebel for use of his equipment and Y. Kawasaki and A. Sugino for generously providing us with anti-Mcm10 antibody. We are grateful to J. Blow for helpful discussions and to S.D. Bell for sharing unpublished data. This work was funded by Cancer Research UK from whom K.L. receives a Senior Cancer Research Fellowship and by the EMBO Young Investigator Programme. A.S.D. received a Marie Curie training fellowship from the European Union and M.K. is funded by a Japan Society for the Promotion of Science (JSPS) postdoctoral fellowship for research abroad.

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  1. Richard C. Jones and Alberto Sanchez-Diaz: These authors contributed equally to this work.

Authors and Affiliations

  1. Cancer Research UK, Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester, M20 4BX, UK

    Agnieszka Gambus, Alberto Sanchez-Diaz, Masato Kanemaki, Frederick van Deursen & Karim Labib

  2. Food and Drug Administration, National Center for Toxicological Research (FDA/NCTR), 3900 NCTR Road, Jefferson, 72079, AR, USA

    Richard C. Jones & Ricky D. Edmondson

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Gambus, A., Jones, R., Sanchez-Diaz, A. et al. GINS maintains association of Cdc45 with MCM in replisome progression complexes at eukaryotic DNA replication forks. Nat Cell Biol 8, 358–366 (2006). https://doi.org/10.1038/ncb1382

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