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  • Original Paper
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Cell cycle regulation of the endogenous wild type Bloom's syndrome DNA helicase

Oncogene volume 19, pages 2731–2738 (2000)Cite this article

Abstract

Bloom's syndrome (BS) is a rare human autosomal recessive disorder characterized by an increased risk to develop cancer of all types. BS cells are characterized by a generalized genetic instability including a high level of sister chromatid exchanges. BS arises through mutations in both alleles of the BLM gene which encodes a 3′–5′ DNA helicase identified as a member of the RecQ family. We developed polyclonal antibodies specific for the NH2- and COOH-terminal region of BLM. Using these antibodies, we analysed BLM expression during the cell cycle and showed that the BLM protein accumulates to high levels in S phase, persists in G2/M and sharply declines in G1, strongly suggestive of degradation during mitosis. The BLM protein is subject to post-translational modifications in mitosis, as revealed by slow migrating forms of BLM found in both demecolcine-treated cells and in mitotic cells isolated from non-treated asynchronous populations. Phosphatase treatment indicated that phosphorylation events were solely responsible for the appearance of the retarded moieties, a possible signal for subsequent degradation. Together, these results are consistent with a role of BLM in a replicative (S phase) and/or post-replicative (G2 phase) process.

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Abbreviations

BS:

Bloom's syndrome

DSB:

double-strand break

SCE:

sister chromatid exchanges

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Acknowledgements

We thank Valérie Schiavon (IFR 54, IGR, Villejuif) and Yann Lécluse (IFR54, IGR, Villejuif) for expert assistance in sorting cells by flow cytometry and in FACS analysis and C Hauss (IGBMC, Illkirch) for technical assistance. We thank Marc Lipinski (CNRS UMR 1598, IGR, Villejuif) for invaluable stimulating discussions and critical reading of the manuscript. We also thank Anne Bahr and Claude Kedinger (IGBMC, Illkirch), Michel Bornens and Bruno Goud (CNRS UMR144, Institut Curie, Paris), Salem Chouaib (INSERM U487, IGFR, Villejuif) and Joëlle Wiels (CNRS UMR 1598, IGR, Villejuif) for their advice and helpful discussions. We are grateful to the anonymous referees for their advice concerning post-translational modifications of the mitotic BLM. This work was supported by funds and/or fellowships from the Centre National de la Recherche Scientifique, the Institut National de la Santé et de la Recherche Médicale, the Centre Hospitalier Universitaire Régional, the Association pour la Recherche sur le Cancer (ARC 9400 and 9660, to Mounira Amor-Guéret, ARC 9479 to Claude Kedinger), the Groupement des Entreprises Françaises dans la Lutte contre le Cancer, the Fondation de France, the Ligue Nationale contre le Cancer and the Université Louis Pasteur de Strasbourg. Stéphanie Dutertre is a recipient of a fellowship from the Ministère de l'Education Nationale, de la Recherche et de la Technologie and Mouna Ababou is a recipient of a fellowship from the Ligue Nationale contre le Cancer (Comité de la Haute-Savoie).

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Authors and Affiliations

  1. Centre National de la Recherche Scientifique, Unité Mixte de Recherche 1598, Institut Gustave Roussy, 39 Rue Camille Desmoulins, 94 805 Villejuif Cedex, France

    Stéphanie Dutertre, Mouna Ababou, Rosine Onclercq, Christian Jaulin & Mounira Amor-Guéret

  2. Laboratoire de Recherche Correspondant No2 du CEA (DSV/DRR, Fontenay aux Roses)/Laboratoire de Radiopathologie, Institut Curie, 26, rue d'Ulm, Paris, 75005, France

    Jozo Delic

  3. Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM/CNRS/ULP, BP 163, 67404 Illkirch Cedex, C.U. de Strasbourg, France

    Bruno Chatton

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  1. Stéphanie Dutertre
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Dutertre, S., Ababou, M., Onclercq, R. et al. Cell cycle regulation of the endogenous wild type Bloom's syndrome DNA helicase. Oncogene 19, 2731–2738 (2000). https://doi.org/10.1038/sj.onc.1203595

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