Repeated sequences, which are very common in genomes, provide additional opportunities for non-allelic homologous recombination (NAHR). These events can lead to genetic alterations such as deletions, inversions, translocations or copy number variation. As a consequence, many human disorders result from genomic rearrangements involving repeated sequences. For example, the Alu repeats, which are present in ~1 million copies in the human genome, have been found at the deletion breakpoints of a considerable number of genes involved in human pathologies. Despite extensive observations that repeated sequences are predisposed to rearrangements, the events leading to these reactions are not fully understood. Here, we explored the possibility that replication stress, a typical threat to cell survival, could trigger recombination between repeats, and identified the genes regulating this process.