Homologous recombination is not enhanced in UV-irradiated normal and repair-deficient human fibroblasts.

Many mammalian cells exhibit damage-inducible phenomena that resemble the bacterial SOS functions. However, whereas RecA plays a prominent role in the prokaryotic SOS response, in mammalian cells so far no enhanced recombination as a result of treatment with DNA-damaging agents of the cells, rather than of infecting viruses, has been found. In order to study recombination as a UV-inducible cellular phenomenon we infected UV-irradiated normal and repair-deficient human fibroblasts with a mixed population of adenovirus 5 (Ad5) mutants that carried a deletion in the E1A or the E2A gene. Wild-type recombinant progeny viruses were readily obtained, but no enhanced recombination was observed at any UV dose given to the cells, nor at any time point between -6 h and +4 days between irradiation and infection. Control experiments, in which we infected unirradiated cells with UV-irradiated Ad5 deletion mutants (a test for recombination targeted at UV-damaged DNA) showed a strong increase in wild-type recombinant viruses when both deletion mutants had been irradiated compared to the additive effect of irradiation of either one of the mutants alone. Therefore, this study shows that UV irradiation results in an enhanced recombination activity in cells that is specifically targeted to damaged DNA, but it does not cause a general (untargeted) recombinational response (enhanced recombination) in the cell.