Models for the repair of DSBs. (A) In the DSBR model, the ends are processed to yield 3′ single-stranded tails. The 3′ ends invade the homologous duplex, priming DNA synthesis. After ligation, a dHJ intermediate is formed, which can subsequently be resolved by endonucleolytic cleavage of the two Holliday junctions to generate crossover or noncrossover products. (B) In the SDSA model, the ends are processed to yield 3′ single-stranded tails, one of which invades the homologous duplex, priming DNA synthesis. The displacement loop (D-loop) formed by strand invasion could be extended by DNA synthesis or could migrate with the newly synthesized DNA. After displacement from the donor duplex, the nascent strand pairs with the other 3′ single-stranded tail and DNA synthesis completes repair. (C) The initial steps in the BIR model are the same as in the SDSA model, but DNA synthesis from the invading strand continues to the end of the DNA molecule. (D) In the SSA model, a DSB made between direct repeats is subject to resection to generate 3′ single-stranded tails. When complementary sequences are revealed due to extensive resection, the single-stranded DNA anneals, resulting in deletion of one of the repeats and the intervening DNA. The 3′ tails are endonucleolytically removed, and the nicks are ligated. The 3′ ends are indicated by arrowheads.