Figure 1.

Model for repair of DNA double-strand breaks by homologous recombination in somatic cells. When a DNA double-strand break (DSB) occurs in a DNA molecule, repair can proceed by multiple pathways largely controlled by end resection. NHEJ is capable of repairing unresected or minimally resected DSBs in a template-independent fashion. MMEJ and single-strand annealing (SSA) rely on different extents of homology between the two DSB ends for repair independent of a donor molecule. Homologous recombination proceeds as shown in the figure using a homologous donor DNA. Most of the extended D-loops in somatic cells are disrupted and subsequently repaired by SDSA. The end result of the repair by SDSA is always a noncrossover outcome, thus avoiding loss of heterozygosity produced by somatic crossovers. SDSA occurs by disruption of the extended D-loop and annealing the newly synthesized DNA with the second end of the broken molecule. Alternatively, the newly synthesized strand may invade the second end as depicted in Fig. S1. The extended D-loop can also undergo second-end capture or invasion (Fig. S2) to form a double Holliday junction (dHJ). This may either lead to a crossover or a noncrossover outcome. Invasion by the second break end makes dHJ formation and hence crossover outcome more likely, as depicted in Fig. S2. See Fig. S3 for another model for crossover generation. dHJs can be dissolved into noncrossovers by the concerted action of the Sgs1–Top3–Rmi1 complex to migrate the two junctions toward each other and then decatenate the strands of the hemicatenane by the Top3 topoisomerase activity. Each colored line indicates a strand of DNA, and dotted lines represent DNA synthesis.