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Polo-like kinase-1 is a target of the DNA damage checkpoint

Nature Cell Biology volume 2, pages 672–676 (2000)Cite this article

Abstract

Polo-like kinases (PLKs) have an important role in several stages of mitosis. They contribute to the activation of cyclin B/Cdc2 and are involved in centrosome maturation and bipolar spindle formation at the onset of mitosis1,2. PLKs also control mitotic exit by regulating the anaphase-promoting complex (APC) and have been implicated in the temporal and spatial coordination of cytokinesis1,2. Experiments in budding yeast have shown that the PLK Cdc5 may be controlled by the DNA damage checkpoint3,4. Here we report the effects of DNA damage on Polo-like kinase-1 (Plk1) in a variety of human cell lines. We show that Plk1 is inhibited by DNA damage in G2 and in mitosis. In line with this, we show that DNA damage blocks mitotic exit. DNA damage does not inhibit the kinase activity of Plk1 mutants in which the conserved threonine residue in the T-loop has been changed to aspartic acid, suggesting that DNA damage interferes with the activation of Plk1. Significantly, expression of these mutants can override the G2 arrest induced by DNA damage. On the basis of these data we propose that Plk1 is an important target of the DNA damage checkpoint, enabling cell-cycle arrests at multiple points in G2 and mitosis.

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Figure 1: DNA damage inhibits Plk1 activity.
Figure 2: DNA damage blocks mitotic exit.
Figure 3: G2 arest induced by DNA damage requires inhibition of Plk1.

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Acknowledgements

We thank H. Piwnica-Worms for providing the Cdc25C plasmids and GST–Cdc25C, O. Kelm and P. Duncan for reagents and comments on the manuscript, S. Pippel for technical assistance and the members of the Jordan laboratory and the Department of Physiological Chemistry for helpful discussions. This work was supported by a grant from the Dutch Cancer Society (UU 96-1176).

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Author notes

  1. Lionel Arnaud

    Present address: Division of Basic Sciences, Fred Hutchinson Cancer Research Centre, 1100 Fairview Avenue North A 2-025, P.O. Box 19024, Seattle, Washington, 98109, USA

  2. Erich A. Nigg

    Present address: Department of Cell Biology, Max-Planck-Institute for Biochemistry, Am Klopferspitz 18a, D-82152, Martinsried, Germany

Authors and Affiliations

  1. Department of Hematology, Jordan Laboratory, University Medical Centre Utrecht, G 03.647, P.O. Box 85500, GA, 3508, Utrecht, The Netherlands

    Veronique A. J. Smits, Rob Klompmaker, Gert Rijksen & René H. Medema

  2. Department of Molecular Biology, Sciences II, 30 Quai Ernest-Ansermet, University of Geneva, Geneva, 4, CH-1211, Switzerland

    Lionel Arnaud & Erich A. Nigg

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Correspondence to René H. Medema.

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Smits, V., Klompmaker, R., Arnaud, L. et al. Polo-like kinase-1 is a target of the DNA damage checkpoint. Nat Cell Biol 2, 672–676 (2000). https://doi.org/10.1038/35023629

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