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Cyclin B2 suppresses mitotic failure and DNA re-replication in human somatic cells knocked down for both cyclins B1 and B2

Oncogene volume 26, pages 7175–7184 (2007)Cite this article

Abstract

Cyclin-dependent kinase 1 (CDK1) plays a crucial role in establishing metaphase and has also been shown to prevent DNA re-replication. Cyclins B1 and B2 are two known activators of CDK1 operating during mitosis in human cells. Little is known about the specific roles of each of these cyclins in CDK1 activation, but cyclin B2 is thought to play a minor role and to be unable to replace cyclin B1 for mitosis completion. In our study, we found that severe reduction by separate RNA interference of either cyclin B1 or cyclin B2 protein levels results in little or no alteration of the cell cycle and, more specifically, of mitosis progression. In contrast, simultaneous depletion of both B-type cyclins leads to massive accumulation of 4N cells, mitotic failure, premature mitosis exit and DNA re-replication. These defects can be corrected by the ectopic expression of a cyclin B2 resistant to the short hairpin RNA. Altogether, these data show that, in cycling human cells, cyclin B2 can compensate for the downregulation of cyclin B1 during mitosis. They also clearly implicate cyclins B1 and B2 as crucial activators of CDK1 in its biological function of DNA re-replication prevention.

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Acknowledgements

We thank Malika Temal for her contribution to the early phase of this project, Françoise Thierry and Moshe Yaniv for providing us a free access to the videomicroscope and flow cytometer. We also thank Stefan Geley for the histone H2B-GFP expression vector and Katja Wassman for the anti-Mad2 antiserum. This work was supported by grants from University Paris 6, CNRS, CNRS programme ‘Protéomique et Ingénierie des Protéines’, contract PGP 03/0676 and IFR 83 ‘Biologie Intégrative’. SB is a fellow from Association pour la Recherche sur le Cancer, and AdG was a fellow from Ministère de la Recherche et de la Technologie.

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  1. S Bellanger

    Present address: 2Current address: Institute of Medical Biology, 61 Biopolis Drive, Proteos Building, Singapore 138673.,

  2. A de Gramont

    Present address: 3Current address: Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD 20892, USA.,

Authors and Affiliations

  1. Laboratoire de Biochimie Cellulaire, CNRS UMR 7098, Université P. & M. Curie – Paris 6, Paris, France

    S Bellanger, A de Gramont & J Sobczak-Thépot

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Correspondence to J Sobczak-Thépot.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Bellanger, S., de Gramont, A. & Sobczak-Thépot, J. Cyclin B2 suppresses mitotic failure and DNA re-replication in human somatic cells knocked down for both cyclins B1 and B2. Oncogene 26, 7175–7184 (2007). https://doi.org/10.1038/sj.onc.1210539

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