synthesisdependent

Synthesis-dependent strand annealing, commonly abbreviated SDSA, is a pathway of homologous recombination used to repair double-strand breaks and other DNA lesions. The term describes a repair sequence in which new DNA synthesis occurs before the damaged ends are joined, reducing the likelihood of crossovers that can lead to chromosomal alterations.

In brief, SDSA begins with resection of the break to produce 3’ single-stranded DNA tails. One 3’ end invades a homologous template and pairs with it to form a displacement loop (D-loop). DNA synthesis then extends the invading end using the template as a guide. After limited synthesis, the newly extended strand is displaced from the template and anneals to the other resected end. Gap-filling DNA synthesis and ligation complete the repair, leaving behind a non-crossovers outcome.

Key features of SDSA include its tendency to produce gene conversion without reciprocal exchange of flanking markers, and its relatively conservative repair compared with pathways that generate crossovers via Holliday junctions. SDSA is thought to be a major mode of mitotic homologous recombination in many organisms, including yeast and plants, and it is regulated by a network of recombination proteins such as Rad51, Rad52, and various helicases and mediators that influence strand invasion, synthesis, and annealing.

SDSA contrasts with other repair routes like double Holliday junction pathways and break-induced replication, which can yield crossovers or extensive DNA synthesis. Understanding SDSA contributes to insights into genetic stability, genome editing outcomes, and meiotic vs. mitotic recombination dynamics.