Speculative mechanisms involved in TALEN induced DSB repair.

<p>Blue lines represent the genome with DSB sites, and clusters of vertical bars indicate the TR region. The DSB ends can be bound by two groups of proteins independently: the binding of DNA-dependent protein kinase (DNA-PK) complex (Ku 70 and Ku80) and the following ligase IV seals the gap by direct rejoin the broken ends, which is termed non-homologous end-joining (NHEJ) pathway (A); While the binding of MRN complex and Exo1 nuclease initiates the 5'-3' resection of the ends, which is followed by either a replication slippage pathway (B) or homologous recombination (HR) pathway (C, D). In the replication slippage pathway, the TR region forms a secondary structure and leads to mispairing between the template and the newly-synthesized DNA strand. In the HR pathway, the 3' overhang invades into the homologous template DNA (red lines) and primes DNA synthesis (dash lines) to form a structure called D-loop, which will result in a double Holliday junction (dHJ). dHJ can either be resolved by strand cleavage with or without crossover, which is referred as classical DSB repair (DSBR) pathway of HR (C), and dHJ can also be dissolved by helicases to generate a non-crossover (D). Alternatively, D-loop can be directly dissociated through a synthesis-dependent strand annealing (SDSA) pathway, which results in exclusively non-crossover products (D).