Irradiation of dominant marker DNA with UV light (150 to 1,000 J/m4) was found to stimulate the transformation of human cells by this marker from two-to more than fourfold. This phenomenon is also displayed by xeroderma pigmentosum cells (complementation groups A and F), which are deficient in the excision repair of UV-induced pyrimidine dimers in the DNA. Also, exposure to UV of the transfected (xeroderma pigmentosum) cells enhanced the transfection efficiency. Removal of the pyrimidine dimers from the DNA by photoreactivating enzyme before transfection completely abolished the stimulatory effect, indicating that dimer lesions are mainly responsible for the observed enhancement. A similar stimulation of the transformation efficiency is exerted by 2-acetoxy-2-acetylaminofiuorene modification of the DNA. No stimulation was found after damaging vector DNA by treatment with DNase or -y rays. These findings suggest that lesions which are targets for the excision repair pathway induce the increase in transformation frequency. The stimulation was found to be independent of sequence homology between the irradiated DNA and the host chromosomal DNA. Therefore, the increase of the transformation frequency is not caused by a mechanism inducing homologous recombination between these two DNAs. UV treatment of DNA before transfection did not have a significant effect on the amount of DNA integrated into the xeroderma pigmentosum genome.UV light induces a variety of lesions into DNA, such as pyrimidine dimers (the main product), thymidine glycols, 6-4 photoproducts, and DNA protein cross-links. Deformation of the DNA double-helix structure by these lesions disturbs essential processes, such as replication and transcription, and ultimately can result in mutagenesis and lethality. The major repair system operating on many of these lesions is the excision repair pathway (see references 19, 22, and 29 for reviews). Irradiation of prokaryotic and eukaryotic cells with UV light and in some cases transfection with DNA exposed to UV light induces a variety of processes, such as stimulation of recombination (13,17,21,23), enhancement of survival of UV-damaged viruses (host cell reactivation; 6, 8, 9, 37) or bacteriophages (Weigle reactivation; 46), enhanced capacity to repair potentially lethal damage (45), and increased mutagenesis (7-9, 12, 37). In Escherichia coli many of these phenomena are part of the pleiotropic SOS response (reviewed in reference 30). In eukaryotes several of these features are expressed concomitantly, and it is likely that they are at least in part related to each other. However, the nature of the inducing signal(s) is still unknown. Here we report that UV irradiation has a stimulatory effect on the genetic transformation of human cells. This phenomenon was encountered in the course of experiments aimed at the cloning of a human DNA repair gene complementing the excision repair defect of xeroderma pigmentosum (XP) cells. The rational of this approach was to rescue a UV-damaged dominant marker when cotransfected...