Eliminating Both Canonical and Short-Patch Mismatch Repair in Drosophila melanogaster Suggests a New Meiotic Recombination Model
(A) A double-strand break (DSB) is processed to form 3′ single strand overhangs. (B) One of the single strands invades the homologous chromosome, forming a single-end invasion intermediate. (C) After synthesis, this intermediate may be disassembled, allowing the newly synthesized DNA to anneal to the other resected end. This process, called synthesis dependent strand annealing (SDSA), generates NCOs only. This NCO is drawn with hDNA intact, but the nicks in the product would likely stimulate mismatch repair, possibly leading to a single tract of gene conversion to one side of the DSB. (D) In the absence of SDSA, the second end of the DSB may be captured by annealing to the displaced strand of the D-loop, priming synthesis. (E) This structure is ligated to form a double Holliday junction (dHJ). The HJs are cleaved in a process called resolution. (F) Cleaving different strands at each junction (left) results in a CO. One way of doing this (open arrowheads) results in products with a single hDNA tract; the other orientation (black arrowheads) gives products with MMR-independent gene conversion (outlined in black) adjacent to the tract of hDNA. (G) Cutting the same two strands at both junctions (right) results in a NCO. Both orientations give one product with a single tract of hDNA and one with hDNA adjacent to a gene conversion tract. Resolution, like SDSA, leaves nicks in the final products that are thought to direct mismatch repair. (H) dHJs may be dissolved by the combined activities of a helicase and topoisomerase, resulting in a NCO with trans hDNA and lacking nicks.