Inactivation of the RAD51 recombination pathway stimulates UV-induced mutagenesis in mammalian cells.
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.
Lambert
Sarah
S
UMR217 CNRS-CEA, CEA, Direction des Sciences du Vivant, Département de Radiobiologie et Radiopathologie, 60-68 avenue du Général Leclerc, 92 265 Fontenay aux Roses, cedex, France.
Lopez
Bernard S
BS
D000818:Animals; D016466:CHO Cells / Q000378:metabolism / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects; D006224:Cricetinae; D004249:DNA Damage / Q000528:radiation effects*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005785:Gene Conversion; D005799:Genes, Dominant / Q000502:physiology; D006801:Humans; D016296:Mutagenesis; D051135:Rad51 Recombinase; D011836:Radiation Tolerance; D011995:Recombination, Genetic / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D004268:DNA-Binding Proteins; C495153:RAD51 protein, human; D051135:Rad51 Recombinase