a Homologous recombination (HR)-mediated DSB repair pathways. HR pathways can be generally classified into three stages: presynapsis, synapsis, and postsynapsis. In presynapsis, single-stranded tails of DSB ends are generated by nucleases (step 1). During synapsis, invasion of the DNA strand by Rad51 cofactors leads to the formation of a D-loop (step 2). At least three distinct pathways, double-strand break repair (DSBR), break-induced replication (BIR), and synthesis-dependent strand annealing (SDSA), share the D-loop intermediate. In DSBR (steps 3a-5a and 5b), DSB ends are engaged, leading to double-Holliday junction (dHJ) formation. A dHJ is a substrate for separation into either noncrossover or crossover products. In SDSA (steps 3b, 4b and 5c), the leader strand is displaced from the D-loop and reannealed with the single-stranded tail, forming noncrossover products. In BIR (steps 3b, 4c, and 5d), the D-loop is assembled into a complete replication fork and copies the entire distal arm of the chromosome. b Electron microscopy images of replication forks in mESCs (modified from Ahuja et al. 3). Arrows indicate ssDNA gaps. D, daughter DNA strand; P, parental DNA strand. The scale bar in the inset is 200 bp.