Figure 2. Pathways of meiotic DSB repair.

During meiosis chromosomes are first replicated (step 1) and the identical sister chromatids (red and blue double lines indicate duplex DNA) are linked together by meiosis-specific cohesins (step 1, gold lines) and additional proteins that form axial elements (step 2, purple ovals). Pairing of homologs leads to formation of the synaptonemal complex (step 3, yellow bars); in D. melanogaster, for example, synapsis occurs independently of DSBs, while in S. cerevisiae synapsis would not occur until step 8. Recombination is initiated by programmed DSBs by Rec12 or Spo11 (Figure 1) and numerous partners (step 4, green circles). The now covalently bound Rec12 or Spo11 is removed and the DNA end is resected to create free 3' DNA ends (step 5). The 3' DNA ends invade either the homolog (step 6) or the sister chromatid (step 6a) to create a displacement loop (D-loop), which is extended by DNA synthesis primed by the invading 3' end (see Figure 1 for details). Rad51- or Dmc1-promoted annealing of the other 3' end (“second end capture,” step 7) and ligation of ends forms a double Holliday junction (dHJ; step 8). A single HJ (sHJ; step 7b) is formed if the D-loop is cleaved before the second end anneals. HJ resolution yields a crossover (CO) or non-crossover (NCO), depending on the orientation of cleavage of the HJ(s) (white arrowheads, step 9). If, however, the D-loop is dissociated and the invading end, previously extended by DNA synthesis, anneals with the other DSB end (step 7a), a NCO is formed; this repair is called synthesis-dependent strand annealing (SDSA). Crossover control can act at steps 6, 7, or 9.