In genetics, the initial processes involved in repair of a double-strand break by synthesis-dependent strand annealing (SDSA) are identical to those in the double Holliday junction model, and have been most extensively studied in yeast species Saccharomyces cerevisiae. Following a double-stranded break, a protein complex (MRX) binds to either end of the break, working with DNA nucleases to carry out resection, resulting in 5' end digest to produce 3' overhangs of single-stranded DNA (see Figure). These overhangs are then bound to form a nucleoprotein filament, which can then locate DNA sequences similar to one of the 3' overhangs, initiating a single-stranded strand invasion into the DNA duplex containing these sequences. Once strand invasion has occurred, a displacement loop, or D-loop, is formed, at which point either SDSA or a double Holliday junction occurs. Homologous recombination via the SDSA pathway occurs in both mitotic and meiotic cells as an important mechanism of non-crossover recombination, and was first suggested as a model in 1976, acquiring its current name in 1994. As the double Holliday junction model was the first posited in order to explain this phenomenon, various versions of the SDSA model were later proposed to explain heteroduplex DNA configurations that did not match predictions of the double Holliday junction model. Studies in S. cerevisiae found that non-crossover products appear earlier than double Holliday junctions or crossover products, which challenged the previous notion that both crossover and non-crossover products are produced by double Holliday junctions . SDSA is unique in that D-loop translocation results in conservative rather than semiconservative replication, as the first extended strand is displaced from its template strand, leaving the homologous duplex intact. Therefore, although SDSA produces non-crossover products because flanking markers of heteroduplex DNA are not exchanged, gene conversion does occur, wherein nonreciprocal genetic transfer takes place between two homologous sequences. The Sgs1 (BLM) helicase is an ortholog of the human Bloom syndrome protein. It appears to be a central regulator of most of the recombination events that occur during S. cerevisiae meiosis. Sgs1(BLM) may disassemble D-loop structures analogous to early strand invasion intermediates and thus promote NCO formation by SDSA. The Sgs1 helicase forms a conserved complex with the topoisomerase III (Top3)-RMI1 heterodimer (that catalyzes DNA single strand passage). This complex, called STR (for its three components), promotes early formation of NCO recombinants by SDSA during meiosis. As reviewed by Uringa et al. the RTEL1 helicase is required to regulate recombination during meiosis in the worm Caenorhabditis elegans. RTEL1 is a key protein in repair of DSBs. It disrupts D-loops and promotes NCO outcomes through SDSA. The number of DSBs created during meiosis can substantially exceed the number of final CO events. In the plant Arabidopsis thaliana, only about 4\% of DSBs are repaired by CO recombination, suggesting that most DSBs are repaired by NCO recombination. Data based on tetrad analysis from several species of fungi show that only a minority (on average about 34\%) of recombination events during meiosis are COs (see Whitehouse,Whitehouse, HLK (1982). Genetic Recombination: understanding the mechanisms. Wiley. p. 321 & Table 38. . Tables 19 and 38 for summaries of data from S. cerevisiae, Podospora anserina, Sordaria fimicola and Sordaria brevicollis). In the fruit fly D. melanogaster during meiosis in females there is at least a 3:1 ratio of NCOs to COs. These observations indicate that the majority of recombination events during meiosis are NCOs, and suggest that SDSA is the principal pathway for recombination during meiosis . The major function of SDSA during meiosis presumably is to repair DNA damages, particularly DSBs, in the genomes to be passed on to gametes (see Genetic recombination) .
Synthesis-dependent strand annealing (SDSA) is a major mechanism of homology-directed repair of DNA double-strand breaks (DSBs). Although many of the features of SDSA were first suggested in 1976, the double-Holliday junction model proposed in 1983 was favored by many researchers. In 1994, studies of double-strand gap repair in Drosophila were found to be incompatible with the double-Holliday junction model, leading researchers to propose a model they called synthesis-dependent strand annealing. Subsequent studies of meiotic recombination in S. cerevisiae found that non-crossover products appear earlier than double-Holliday junctions or crossover products, challenging the previous notion that both crossover and non-crossover products are produced by double-Holliday junctions and leading the authors to propose that non-crossover products are generated through SDSA . SDSA is unique in that D-loop translocation results in conservative rather than semiconservative replication, as the first extended strand is displaced from its template strand, leaving the homologous duplex intact. Therefore, although SDSA produces non-crossover products because flanking markers of heteroduplex DNA are not exchanged, gene conversion may occur, wherein nonreciprocal genetic transfer takes place between two homologous sequences. Divergence between SDSA and double-Holliday junction occurs when the D-loop is disassembled allow the nascent strand to anneal to other resected end of the DSB (in the double-Holliday junction model the strand displaced by D-loop extension anneals to the other end of the DSB in "2nd end capture"). Research in Drosophila melanogaster identified the Bloom syndrome helicase (Blm) as the enzyme promoting dissassembly of the D-loop. Similarly, S. cerevisiae Sgs1 , an ortholog of BLM, appears to be a central regulator of most of the recombination events that occur during S. cerevisiae meiosis. Sgs1(BLM) may disassemble D-loop structures analogous to early strand invasion intermediates and thus promote NCO formation by SDSA. The Sgs1 helicase forms a conserved complex with the topoisomerase III (Top3)-RMI1 heterodimer (that catalyzes DNA single strand passage). This complex, called STR (for its three components), promotes early formation of NCO recombinants by SDSA during meiosis. As reviewed by Uringa et al. the RTEL1 helicase is proposed to regulate recombination during meiosis in the worm Caenorhabditis elegans. RTEL1 is a key protein in repair of DSBs. It disrupts D-loops and is though to promote NCO outcomes through SDSA. The number of DSBs created during meiosis can substantially exceed the number of final CO events. In the plant Arabidopsis thaliana, only about 4\% of DSBs are repaired by CO recombination, suggesting that most DSBs are repaired by NCO recombination. Data based on tetrad analysis from several species of fungi show that only a minority (on average about 34\%) of recombination events during meiosis are COs (see Whitehouse,Whitehouse, HLK (1982). Genetic Recombination: understanding the mechanisms. Wiley. p. 321 & Table 38. . Tables 19 and 38 for summaries of data from S. cerevisiae, Podospora anserina, Sordaria fimicola and Sordaria brevicollis). In the fruit fly D. melanogaster during meiosis in females there is at least a 3:1 ratio of NCOs to COs. These observations indicate that the majority of recombination events during meiosis are NCOs, and suggest that SDSA is the principal pathway for recombination during meiosis .
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