Long-Distance Relationships: Suppression of Repeat-Mediated Deletions

A critical initial decision on how to repair a DSB involves whether to utilize canonical nonhomologous end joining (c-NHEJ) that typically creates small mutations, or a number of alternative pathways that first require DNA resection to expose a long stretch of single-stranded DNA around the breaks (Figure 1). These resected segments can then participate in homologous recombination (HR), which is the most conservative repair pathway, alternative nonhomologous end joining (altNHEJ), or single-strand annealing (SSA)-like mechanisms that typically create significant deletions (reviewed in [2]). The DSB repair pathway utilized will influence the nature of damage to the genome. These pathways are regulated by a number of factors, including the stage of the cell cycle, as well as the expression of many of the proteins that sense the damage or participate in the repair pathways (Figure 1) [1]. The choice of repair pathways that utilize resection can also be influenced by the presence of repetitive DNA sequences in the vicinity of the DSB, as thesemay interact with the exposed single-stranded regions. Although this will primarily be in the SSA subpathway, HRmayalsocontribute if there are non-allelic sequences (Figure 1).