Inactivation of the RAD51 recombination pathway stimulates UV-induced mutagenesis in mammalian cells

Abstract
We have examined the impact of the RAD51 recombination pathway on recombination and mutagenesis induced by UV-C in mammalian cells. We used hamster CHO cell lines that express different forms of Rad51 protein, resulting in stimulation or inhibition of spontaneous gene conversion. Spontaneous mutagenesis was affected by none of the RAD51 forms. The wild-type mouse MmRAD51 affects neither UV-induced recombination nor UV-induced mutagenesis. In contrast, the dominant negative SMRAD51 strongly impairs UV-induced recombination while it stimulates UV-induced mutagenesis. Our results show that a defect in the RAD51 gene conversion pathway reveals (a) mutagenic alternative pathway(s) to repair UV-damage, in mammalian cells.