Repair of DNA double-strand breaks by DSBR and SDSA.
Double-strand breaks (DSBs) can be repaired by several homologous recombination (HR)-mediated pathways, including double-strand break repair (DSBR) and synthesis-dependent strand annealing (SDSA). a | In both pathways, repair is initiated by resection of a DSB to provide 3' single-stranded DNA (ssDNA) overhangs. Strand invasion by these 3' ssDNA overhangs into a homologous sequence is followed by DNA synthesis at the invading end. b |After strand invasion and synthesis, the second DSB end can be captured to form an intermediate with two Holliday junctions (HJs). After gap-repair DNA synthesis and ligation, the structure is resolved at the HJs in a non-crossover (black arrow heads at both HJs) or crossover mode (green arrow heads at one HJ and black arrow heads at the other HJ). c | Alternatively, the reaction can proceed to SDSA by strand displacement, annealing of the extended single-strand end to the ssDNA on the other break end, followed by gap-filling DNA synthesis and ligation. The repair product from SDSA is always non-crossover.
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How does DNA recombination work? It occurs frequently in many different cell types, and it has important implications for genomic integrity, evolution, and human disease.
