Mutagenesis in mammalian cells induced by triple helix formation and transcription-coupled repair

When mammalian cells were treated with tripler-forming oligonucleotides of sufficient binding affinity, mutations were specifically induced in a simian virus 40 vector contained within the cells. Tripler-induced mutagenesis was not detected in xeroderma pigmentosum group A cells nor in Cockayne's syndrome group B cells, indicating a requirement for excision repair and for transcription-coupled repair, respectively, in the process. Tripler formation was also found to stimulate DNA repair synthesis in human cell extracts, in a pattern correlating with the inhibition of transcription in such extracts. These findings may have implications for therapeutic applications of tripler DNA and raise the possibility that naturally occurring triple helices are a source of genetic instability.