Regulation of Single-Strand Annealing and its Role in Genome Maintenance

Single-strand annealing (SSA) is a DNA double-strand break (DSB) repair pathway that uses homologous repeats to bridge DSB ends. SSA involving repeats that flank a single DSB causes a deletion rearrangement between the repeats, and hence is relatively mutagenic. Nevertheless, this pathway is conserved, in that SSA events have been found in several organisms. In this review, we describe the mechanism of SSA and its regulation, including the cellular conditions that may favor SSA versus other DSB repair events. We will also evaluate the potential contribution of SSA to cancer-associated genome rearrangements, and to DSB-induced gene targeting.

TrendsThe SSA DSB repair pathway causes a rearrangement between two homologous repeats.SSA and ALT-EJ are similar, as they both involve an annealed intermediate to synapse a DSB, but show mechanistic distinctions, including differential requirements for RAD52 versus PARP and Polθ.End resection to generate 3′ ssDNA is a pivotal step of SSA, and is a shared intermediate with HDR and ALT-EJ, but each of these events likely require distinct degrees of end resection. Also, if end resection occurs prior to sister chromatid synthesis, which is the preferred template for HDR, then SSA or ALT-EJ may be required for repair.The relative role of SSA versus ALT-EJ on repeat-mediated rearrangements is affected by the degree of divergence between the repeats.Most gene targeting events are mediated by HDR (i.e., RAD51-dependent), however, some targeting approaches appear to involve SSA or ALT-EJ.