RANDOM-WALK MODELS FOR DNA SYNAPSIS BY RESOLVASE

During site-specific recombination by resolvase, the protein binds to two sites on a supercoiled DNA molecule and the loaded sites then inte ract with each other to form a synaptic complex. The kinetics of synap sis show non-exponential behaviour extending over five log units of ti me and are independent of the length of the DNA molecule and the lengt h of DNA between the sites. In this study, numerical models were devel oped in order to account for how fluctuations in the structure of supe rcoiled DNA might lead to the juxtaposition of distant sites in a mann er consistent with the experimental data on synapsis by resolvase. Mod els where the juxtaposition arises from fluctuations around branch poi nts in the superhelix failed to match the data: they yielded non-expon ential kinetics but only over two log units of time and they predicted longer synapsis times for both larger DNA molecules and larger inter- site spacings. In another model, one fraction of the juxtaposition eve nts gives rise directly to the productive complex while the remaining fraction initially yields a non-productive complex: the latter molecul es undergo no further fluctuations until the abortive synapse dissocia tes at the end of a delay period. This model again failed to match the experimental data. However, the inclusion of three sorts of non-produ ctive complexes, each with a different delay constant, led to progress curves that concurred with the data. Schemes were also developed to a ccount for the juxtaposition of three sites at a branch point in super coiled DNA. (C) 1997 Academic Press Limited.