Homology-dependent interactions in phage lambda site-specific recombination.

General recombination shows a dependence on large regions of homology between the two participating segments of DNA. Many site-specific recombination systems also exhibit a dependence on homology, although in these systems the requirement is limited to a short region (less than 10 base pairs (bp]. We have used the in vitro phage lambda integration reaction to study the role of homology in this model site-specific recombination system. We find that certain non-homologous pairings which are strongly blocked for complete recombination, nevertheless make one pair of strand-exchanges to generate a joint molecule of the Holliday structure type. This result rules out recombination models in which the only homology-dependent step is synapsis (the juxtaposing of the two recombination sites). Our results also reveal a functional asymmetry in the recombination sites. We present models for bacteriophage lambda integrative recombination which accommodate these findings.