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Centrosome duplication in mammalian somatic cells requires E2F and Cdk2–Cyclin A

Nature Cell Biology volume 1, pages 88–93 (1999)Cite this article

Abstract

Centrosome duplication is a key requirement for bipolar spindle formation and correct segregation of chromosomes during cell division. In a manner highly reminiscent of DNA replication, the centrosome must be duplicated once, and only once, in each cell cycle. How centrosome duplication is regulated and coordinated with other cell-cycle functions remains poorly understood. Here, we have established a centrosome duplication assay using mammalian somatic cells. We show that centrosome duplication requires the activation of E2F transcription factors and Cdk2–cyclin A activity.

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Figure 1: Centrosome duplication assay.
Figure 2: Overexpression of p16INK4 blocks centrosome duplication.
Figure 3: Centrosome duplication is dependent on Rb phosphorylation and E2F activity.
Figure 4: Centrosome duplication requires Cdk2–cyclin A activity.
Figure 5: Rescue of DNA replication in RbΔCdk-expressing cells by Cdk2–cyclin E.
Figure 6: Regulation of centrosome duplication in somatic cells.

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Acknowledgements

We thank Y.-D. Stierhof for the electron microscopic data in Fig. 1, N. Roggli for help with artwork, and several colleagues for kind gifts of plasmids, particularly E. Harlow for Cdk1, 2 and 3, J. Massagué for p27Kip1, S. Reed for cyclin E , J. Pines for cyclin A , C.-L. Wu for DP1, and K. Helin for E2F. We also thank B. Amati as well as all members of the laboratory for stimulating discussions. This work was supported by grants from the Swiss National Science Foundation, the Swiss Cancer League, the Human Frontier Science Program and the Canton of Geneva.

Correspondence and requests for materials should be addressed to E.A.N.

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Authors and Affiliations

  1. Department of Molecular Biology, University of Geneva, 30 quai Ernest-Ansermet, Geneva 4, CH-1211, Switzerland

    Patrick Meraldi, Andrew M. Fry & Erich A. Nigg

  2. Institute of Cancer Biology Department of Cell Cycle and Cancer, Danish Cancer Society, Strandboulevarden 49, Copenhagen Ø, DK-2100, Denmark

    Jiri Lukas & Jiri Bartek

  3. Department of Biochemistry, Adrian Building, University of Leicester, University Road, Leicester, LE1 7RH, UK

    Andrew M. Fry

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Correspondence to Erich A. Nigg.

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Meraldi, P., Lukas, J., Fry, A. et al. Centrosome duplication in mammalian somatic cells requires E2F and Cdk2–Cyclin A. Nat Cell Biol 1, 88–93 (1999). https://doi.org/10.1038/10054

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