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DNA double strand break repair and chromosomal translocation: Lessons from animal models

Oncogene volume 20, pages 5572–5579 (2001)Cite this article

Abstract

The maintenance of genomic stability is one of the most important defenses against neoplastic transformation. This objective must be accomplished despite a constant barrage of spontaneous DNA double strand breaks. These dangerous lesions are corrected by two primary pathways of double strand break repair; non homologous end joining and homologous recombination. Recent studies employing mouse models have shown that absence of either pathway leads to genomic instability, including potentially oncogenic translocations. Because translocations involve the union of different chromosomes, cellular machinery must exist that creates these structures in the context of unrepaired double strand breaks. Evidence is mounting that the pathways of double strand break repair that are so important for survival may themselves be the culprits that generate potentially fatal translocations. Evidence and models for the dual roles of double strand break repair in both preventing, and generating, oncogenic karyotypic changes are discussed.

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Authors and Affiliations

  1. Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, Massachusetts, USA

    Frederick W Alt

  2. The Children's Hospital, Harvard Medical School, Boston, MA 02115, Massachusetts, USA, USA

    Frederick W Alt

  3. The Center for Blood Research, Harvard Medical School, Boston, MA 02115, Massachusetts, USA

    David O Ferguson & Frederick W Alt

  4. Department of Genetics, Harvard Medical School, Boston, MA 02115, Massachusetts, USA

    Frederick W Alt

  5. Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, Massachusetts, USA

    David O Ferguson

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Correspondence to Frederick W Alt.

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Ferguson, D., Alt, F. DNA double strand break repair and chromosomal translocation: Lessons from animal models. Oncogene 20, 5572–5579 (2001). https://doi.org/10.1038/sj.onc.1204767

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