The Single-Strand Annealing Mechanism Functions at Some Double-Strand Breaks

KEY CONCEPTS
-Single-strand annealing (SSA) occurs at double-strand breaks between direct repeats.
- Resection of double-strand break ends results in 3′– single-stranded tails.
- Complementarity between the repeats allows for annealing of the single strands.
- The sequence between the direct repeats is deleted after SSA is completed.
Some homologous recombination events to repair double- strand breaks are not dependent on strand invasion, D-loop formation, or the proteins that promote these processes. In order to account for these recombination events, which typically take place between direct repeats (repeat sequences that are oriented in the same direction), a model has been devised in which homology between single-strand overhangs is used to direct recombination (see FIGURE 1). When a DSB occurs between two direct repeats, the ends are resected to give single strands. When resection proceeds to the repeat sequences such that the 3′–single-strand tails are homologous, the single strands can anneal. Processing and ligation of the 3′ ends then seals the DSB. As shown in Figure 1, this resection, followed by annealing, eliminates the sequence between the two direct repeats and leaves only one copy of the repeated sequence. Some human diseases arise from the loss of the sequence between the direct repeats, presumably through a single-strand annealing (SSA) mechanism. These diseases include insulin-dependent diabetes, Fabry disease, and α-thalassemia.

FIGURE 1. The single-strand annealing model of homologous recombination. A double-strand break occurs between direct repeats, depicted as red arrows. Following end processing to form single-strand tails with 3′–OH ends, the single strands anneal by homology at the red arrows. The single-strand tails are removed by endonucleases that recognize branch structures. The end product is double-strand break repair with a deletion of the sequences between the repeats and loss of one repeat sequence.