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

To directly determine whether recombinational repair of double-strand break s (DSBs) can occur between heterologous chromosomes and lead to chromosomal rearrangements in mammalian cells, we employed an ES cell system to analyz e 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 conver sion in which a small amount of sequence information was transferred from t he unbroken chromosome onto the broken chromosome. The remaining recombinan ts transferred a larger amount of information, but still no chromosomal abe rrations were apparent. Thus, mammalian cells are capable of searching geno me-wide for sequences that are suitable for DSB repair. The lack of crossov er events that would have led to translocations supports a model in which r ecombination is coupled to replication.