Figure 1.

DSB repair strategies. Blue, double-stranded DNA (dsDNA) molecule; orange, dsDNA template (sister chromatid or homologous chromosome). (A) A DSB occurs in the blue DNA molecule. (B) 5′ resection marks the first step of HDR and results in 3′ ssDNA tails. (C) Rad51-coated ssDNA tail invades a template duplex, displacing one strand to create a D-loop, and primes synthesis. (D) The D-loop is disassembled and a complementarity test between the opposing ends of the break occurs. (E) SDSA is defined by annealing between complementary sequences, followed by trimming and/or gap filling. (F) Ligation restores an intact duplex DNA molecule. Alternative strategies (dotted arrows): (G) cNHEJ can occur instead of resection, which directly ligates the ends and can generate small insertions and deletions (pink segment). (H) MMEJ (catalyzed by DNA polymerase θ in metazoans) can occur prior to strand exchange or after failure to find or anneal at complementary sequences. (I) MMEJ/TMEJ will usually generate a deletion or insertion (pink segment). (J) If the DSB occurs between two direct repeats, complementary sequences may be exposed during resection, and annealing can occur without synthesis, called SSA. (K) SSA results in deletion of one repeat. (L) Second-end capture (annealing of the opposing strand to the D-loop, allowing for extension of that strand) can occur during synthesis. (M) Ligation to the opposing 5′ ends creates a dHJ. (N) Dissolution of the dHJ involves migration of the junctions toward each other and decatenation via topoisomerase activity to (O) restore the DNA molecule. (P) Resolution involves endonucleolytic cleavage of the junctions which can be cut in either orientation, resulting in both (O) noncrossover (restoration of the DNA molecule) and (Q) crossover (recombinant) products.