Recombination between Two Chromosomes: Implications for Genomic Integrity in Mammalian Cells

Genetic integrity relies on the faithful repair of DNAdamage such as double-strand breaks (DSBs). Aberrantrepair of these lesions is expected to result in chromosomal rearrangements, including translocations, that are associated with numerous tumors (Rabbitts 1994; Mitelmanet al. 1997). Models predict that some translocations arisefrom DSB-induced recombination in differentiating lymphoid cell types (Lewis 1994; Hiom et al. 1998) or fromaberrant repair of DNA damage induced by irradiation orother agents (Cornforth and Bedford 1993; Ikeda 1995;Wang et al. 1997). Recently, a genetic system has beendeveloped to study the etiology of these events in mammalian cells (Richardson and Jasin 2000). This system relies on the expression of the rare-cutting I-SceI endonuclease (Jasin 1996) and the strategic placement of I-SceIcleavage sites in the genome to introduce DSBs at predetermined genomic locations. With this system, it has beenshown that two DSBs are sufficient to cause reciprocalchromosomal translocations, even in repair-proficientcells (Richardson and Jasin 2000)...