DNA double strand break repair and chromosomal translocation: Lessons fromanimal models

The maintenance of genomic stability is one of the most important defenses against neoplastic transformation. This objective must be accomplished desp ite a constant barrage of spontaneous DNA double strand breaks. These dange rous lesions are corrected by two primary pathways of double strand break r epair; non homologous end joining and homologous recombination. Recent stud ies employing mouse models have shown that absence of either pathway leads to genomic instability, including potentially oncogenic translocations. Bec ause translocations involve the union of different chromosomes, cellular ma chinery must exist that creates these structures in the context of unrepair ed double strand breaks. Evidence is mounting that the pathways of double s trand break repair that are so important for survival may themselves be the culprits that generate potentially fatal translocations. Evidence and mode ls for the dual roles of double strand break repair in both preventing, and generating, oncogenic karyotypic changes are discussed.