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Maximal chromosome compaction occurs by axial shortening in anaphase and depends on Aurora kinase

Nature Cell Biology volume 9, pages 822–831 (2007)Cite this article

Abstract

Eukaryotic cells must first compact their chromosomes before faithfully segregating them during cell division. Failure to do so can lead to segregation defects with pathological consequences, such as aneuploidy and cancer1,2. Duplicated interphase chromosomes are, therefore, reorganized into tight rods before being separated and directed to the newly forming daughter cells3. This vital reorganization of chromatin remains poorly understood. To address the dynamics of mitotic condensation of single chromosomes in intact cells, we developed quantitative assays based on confocal time-lapse microscopy of live mammalian cells stably expressing fluorescently tagged core histones. Surprisingly, maximal compaction was not reached in metaphase, but in late anaphase, after sister chromatid segregation. We show that anaphase compaction proceeds by a mechanism of axial shortening of the chromatid arms from telomere to centromere. Chromatid axial shortening was not affected in condensin-depleted cells, but depended instead on dynamic microtubules and Aurora kinase. Acute perturbation of this compaction resulted in failure to rescue segregation defects and in multilobed daughter nuclei, suggesting functions in chromosome segregation and nuclear architecture.

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Figure 1: Large-scale chromatin compaction in late anaphase.
Figure 2: Anaphase chromosome compaction by chromatid axial shortening.
Figure 3: Anaphase chromatid arm shortening requires dynamic microtubules and active Aurora B.
Figure 4: Midspindle localization of Aurora B in early anaphase requires dynamic microtubules.
Figure 5: Resolution of segregation defects in condensin-depleted cells depends on dynamic anaphase microtubules.

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Acknowledgements

MeCP2–EGFP was a kind gift from C. Cardoso. The anti-Aurora B antibody was a kind gift from J. M. Peters. We thank P. Lénart, M. Schuh, L. Sironi and J. M. Peters for fruitful discussions and critical reading of the manuscript. F.M.-B. was supported by the German Research Council (DFG EL 246/2-1/2) within the EuroDYNA European Science Foundation network (ESF 03-DYNA-F-29). D.G. was supported by a fellowship from the European Molecular Biology Organization (EMBO).

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  1. Daniel Gerlich

    Present address: Current address: Institute of Biochemistry, Schafmattstrasse 18 ETH-Hönggerberg, HPM E17.2 CH-8093, Zürich, Switzerland.,

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  1. Gene Expression and Cell Biology/Biophysics Units, European Molecular Biology Laboratory, Meyerhofstr. 1, Heidelberg, 69117, Germany

    Felipe Mora-Bermúdez, Daniel Gerlich & Jan Ellenberg

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Correspondence to Jan Ellenberg.

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Mora-Bermúdez, F., Gerlich, D. & Ellenberg, J. Maximal chromosome compaction occurs by axial shortening in anaphase and depends on Aurora kinase. Nat Cell Biol 9, 822–831 (2007). https://doi.org/10.1038/ncb1606

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