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Cell-type-specific replication initiation programs set fragility of the FRA3B fragile site

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  • Anne Letessier

    (Institut Curie, Centre de Recherche, 26 rue d’Ulm, 75248 Paris, France
    UPMC Univ. Paris 06, F-75005 Paris, France
    CNRS UMR 3244, F-75248 Paris, France)

  • Gaël A. Millot

    (Institut Curie, Centre de Recherche, 26 rue d’Ulm, 75248 Paris, France
    UPMC Univ. Paris 06, F-75005 Paris, France
    CNRS UMR 3244, F-75248 Paris, France)

  • Stéphane Koundrioukoff

    (Institut Curie, Centre de Recherche, 26 rue d’Ulm, 75248 Paris, France
    UPMC Univ. Paris 06, F-75005 Paris, France
    CNRS UMR 3244, F-75248 Paris, France)

  • Anne-Marie Lachagès

    (Institut Curie, Centre de Recherche, 26 rue d’Ulm, 75248 Paris, France
    UPMC Univ. Paris 06, F-75005 Paris, France
    CNRS UMR 3244, F-75248 Paris, France)

  • Nicolas Vogt

    (Institut Curie, Centre de Recherche, 26 rue d’Ulm, 75248 Paris, France
    UPMC Univ. Paris 06, F-75005 Paris, France
    CNRS UMR 3244, F-75248 Paris, France)

  • R. Scott Hansen

    (University of Washington School of Medicine)

  • Bernard Malfoy

    (Institut Curie, Centre de Recherche, 26 rue d’Ulm, 75248 Paris, France
    UPMC Univ. Paris 06, F-75005 Paris, France
    CNRS UMR 3244, F-75248 Paris, France)

  • Olivier Brison

    (Institut Curie, Centre de Recherche, 26 rue d’Ulm, 75248 Paris, France
    UPMC Univ. Paris 06, F-75005 Paris, France
    CNRS UMR 3244, F-75248 Paris, France)

  • Michelle Debatisse

    (Institut Curie, Centre de Recherche, 26 rue d’Ulm, 75248 Paris, France
    UPMC Univ. Paris 06, F-75005 Paris, France
    CNRS UMR 3244, F-75248 Paris, France)

Abstract

The origins of fragility Some chromosomal locations, known as common fragile sites, are predisposed to breakage. These sites have pathological relevance because they are often associated with chromosomal translocations. An analysis of the replication dynamics along a 1.6-Mb region of FRA3B, a common fragile site in human lymphocytes that hosts the FHIT tumour suppressor gene, shows that, rather than breakage being due to replication stalling, FRA3B site fragility results from an unusually low density of replication origins. Surprisingly, fragility is cell-type-specific, which may have implications for current models of translocations and tumorigenesis.

Suggested Citation

  • Anne Letessier & Gaël A. Millot & Stéphane Koundrioukoff & Anne-Marie Lachagès & Nicolas Vogt & R. Scott Hansen & Bernard Malfoy & Olivier Brison & Michelle Debatisse, 2011. "Cell-type-specific replication initiation programs set fragility of the FRA3B fragile site," Nature, Nature, vol. 470(7332), pages 120-123, February.
    • Handle: RePEc:nat:nature:v:470:y:2011:i:7332:d:10.1038_nature09745
    DOI: 10.1038/nature09745
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    Cited by:

    1. Thomas E. Wilson & Samreen Ahmed & Amanda Winningham & Thomas W. Glover, 2024. "Replication stress induces POLQ-mediated structural variant formation throughout common fragile sites after entry into mitosis," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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