Robin Holliday proposed a model for HR in meiosis. According to this model, recombination begins after DNA replication. An endonuclease is proposed to introduce a single nick into each duplex so that strands with the same orientation in each duplex are nicked at the same site. Next, symmetric exchange of single DNA strands between duplexes occurs to form what is called symmetric het eroduplex DNA. The crossed strand structure is an important intermediate and is called the Holliday junction. This structure has four-way symmetry and can move down the paired chromatids by a process called branch migration, forming more heteroduplex DNA. At some point, the Holliday Junction structure is cleaved to generate two separate nicked duplexes, a process known as resolution. Because the Holliday junction has four-way symmetry, it can be resolved in an east-west direction, giving noncrossover products, or in a north-south direction, giving crossover products. Mismatch repair of the heteroduplex DNA region can either restore the original genotype or change the genotype of one (e. g., A)to the other (e. g., a). This change gives a 1:3 (or 3:1) segregation and explains the association of gene conversion with crossovers in the flanking region.
The Holliday model has several shortcomings. As described below, recombination is now known to begin at a double-strand break or single-strand gap in one DNA molecule. Furthermore, even though extensive efforts have been made to detect an endonuclease with the specificity required by the model, no such enzyme has been found in eukaryotes although much progress has been made in identifying biochemical resolution activities. Despite these shortcomings, the Holliday model has made an important contribution to our understanding of DNA recombination and several features of the model, including the heteroduplex DNA intermediate, branch migration, the Holliday junction, and resolution, remain an important part of the models that followed.