Double-strand break repair by interchromosomal recombination: suppression of chromosomal translocations

Abstract

To directly determine whether recombinational repair of double-strand breaks (DSBs) can occur between heterologous chromosomes and lead to chromosomal rearrangements in mammalian cells, we employed an ES cell system to analyze recombination between repeats on heterologous chromosomes. We found that recombination is induced at least 1000-fold following the introduction of a DSB in one repeat. Most (98%) recombinants repaired the DSB by gene conversion in which a small amount of sequence information was transferred from the unbroken chromosome onto the broken chromosome. The remaining recombinants transferred a larger amount of information, but still no chromosomal aberrations were apparent. Thus, mammalian cells are capable of searching genome-wide for sequences that are suitable for DSB repair. The lack of crossover events that would have led to translocations supports a model in which recombination is coupled to replication.

Dynamic structure of the SPANX gene cluster mapped to the prostate cancer susceptibility locus HPCX at Xq27

“…The analysis revealed that SPANX-C is derived from SPANX-B by gene conversion-associated additional transfer of adjacent sequences (Fig. 3), as has been proposed previously for other regions by Richardson and co-authors (Richardson et al 1998;Richardson and Jasin 2000). A sequence comparison also demonstrated a role of interspersed repeats (such as LINE1 and Alu) in generating SDs ( Figs.…”

In vivoandin vitrostudies of immunoglobulin gene somatic hypermutation

“…It is usually not possible to infer with complete accuracy the site of V gene incision from the TdT insert because the latter are often associated with sequence deletions. (Richardson & Jasin 2000;Richardson et al 1998). Thus, it might be expected that both a hypermutation associated break and a simultaneous break outside the immunoglobulin locus is required to induce translocation.…”

The Role of the BRCA1 Tumor Suppressor in DNA Double-Strand Break Repair

“…If there is loss of sequence at the site of the break, the resulting junction is often mediated by a region of microhomology, up to 8 bp in size. Homologous recombination can also occasionally introduce errors in sequence by crossover events, but crossover products are actively suppressed in mitotic mammalian cells (25,26). An intermediate type of repair, known as single-strand annealing that is independent of the Rad51 protein, is primarily involved in homologous recombination and can use sequence homology within a single chromosome.…”