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Mechanism limiting centrosome duplication to once per cell cycle

Nature volume 442, pages 947–951 (2006)Cite this article

Abstract

The centrosome organizes the microtubule cytoskeleton and consists of a pair of centrioles surrounded by pericentriolar material. Cells begin the cell cycle with a single centrosome, which duplicates once before mitosis. During duplication, new centrioles grow orthogonally to existing ones and remain engaged (tightly opposed) with those centrioles until late mitosis or early G1 phase, when they become disengaged1. The relationship between centriole engagement/disengagement and centriole duplication potential is not understood, and the mechanisms that control these processes are not known. Here we show that centriole disengagement requires the protease separase2 at anaphase, and that this disengagement licences centriole duplication in the next cell cycle. We describe an in vitro system using Xenopus egg extract and purified centrioles in which both centriole disengagement and centriole growth occur. Centriole disengagement at anaphase is independent of mitotic exit and Cdk2/cyclin E activity, but requires the anaphase-promoting complex and separase. In contrast to disengagement, new centriole growth occurs in interphase, is dependent on Cdk2/cyclin E, and requires previously disengaged centrioles. This suggests that re-duplication of centrioles within a cell cycle is prevented by centriole engagement itself. We propose that the ‘once-only’ control of centrosome duplication is achieved by temporally separating licensing in anaphase from growth of new centrioles during S phase. The involvement of separase in both centriole disengagement and sister chromatid separation would prevent premature centriole disengagement before anaphase onset, which can lead to multipolar spindles and genomic instability3,4.

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Figure 1: Centriole disengagement activity is present in late mitosis.
Figure 2: Molecular requirements for centriole disengagement.
Figure 3: Separase is essential for centriole disengagement.
Figure 4: Centriole disengagement is required for centriole growth.

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Acknowledgements

We thank H. Zou for the non-degradable securin construct; P. Jackson for the D-box peptide and the Δ34Xic1 construct; L. Rose for comments on the manuscript; and J. Lüders for helpful discussions. This work was supported by a grant to T.S. from the National Institutes of Health. M.-F.B.T. is a fellow supported by the Damon-Runyon Cancer Research Foundation.

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  1. Department of Biological Sciences, Stanford University, Department of Genetics, Stanford University Medical School, Stanford, California, 94305-5020, USA

    Meng-Fu Bryan Tsou & Tim Stearns

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  1. Meng-Fu Bryan Tsou
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  2. Tim Stearns
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Correspondence to Tim Stearns.

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Supplementary information

Supplementary Figure 1

Centriole configuration in the cell cycle. (PDF 361 kb)

Supplementary Figure 2

A model for regulation of centrosome duplication. (PDF 99 kb)

Supplementary Figure Legends

Text to accompany the above Supplementary Figures. (DOC 28 kb)

Supplementary Methods

This file contains additional details of the methods used in this study. (DOC 69 kb)

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Tsou, MF., Stearns, T. Mechanism limiting centrosome duplication to once per cell cycle. Nature 442, 947–951 (2006). https://doi.org/10.1038/nature04985

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