A probabilistic model for genetic recombination of nonreplicating lambda-phage DNA, stimulated by "mismatch repair" of UV photoproducts.

Genetic recombination of nonreplicating phage lambda-DNA, during infection of homoimmune lysogenic bacteria, was previously observed to be dramatically stimulated by prior uv irradiation of the phages, even when the Escherichia coli hosts lacked the major uv-photo-product excision-repair system (UvrABC). UvrABC-independent recombination of circular phage molecules depends on host MutHLS functions and on undermethylation of adenines at GATC sites in the phage DNA, and thus appears to be the result of "mismatch repair" of uv photoproducts. Recombinant frequencies pass through a relatively sharp maximum at 20 J/m2 and decrease at higher doses, whereas most plausible models for the process predict monotonic increases with dose, or a plateau at high uv doses. A uv-dose-dependent loss of biological activity (restriction) of all intracellular phage DNA was also observed previously. In order to provide a framework for testing possible explanations for the unusual recombinant-frequency vs uv-dose curve, a statistical model was constructed. This model includes probability terms for all possible one-exchange and two-exchange recombination processes, and incorporates the assumption that dimer recombinants are more susceptible to restriction than monomer parents (or recombinants), because of their larger target size. By adjustment of model parameters, particularly epsilon, the efficiency per photoproduct of initiation of a recombinational exchange, a theoretical dose-response curve that agreed well with experiment was obtained. The best fit corresponded to epsilon = 0.035, close to the previously observed restriction efficiency of 0.053. In the calculations, the value for h0, the average length of heteroduplex DNA, was taken to be 0.5 lambda units, i.e., about 25 kilobase pairs. This estimate for h0 was obtained here by analysis of the density distributions of the progeny of crosses between nonreplicating density-labeled lambda-phage chromosomes, published by others [M. S. Fox, C. S. Dudney and E. J. Sodergren (1979) Cold Spring Harbor Symposium on Quantitative Biology, Vo. 43, pp. 999-1007].