Mutagenesis in mammalian cells induced by triple helix formation and transcription-coupled repair.
When mammalian cells were treated with triplex-forming oligonucleotides of sufficient binding affinity, mutations were specifically induced in a simian virus 40 vector contained within the cells. Triplex-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. Triplex 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 triplex DNA and raise the possibility that naturally occurring triple helices are a source of genetic instability.
Wang
G
G
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520-8040, USA.
Seidman
M M
MM
Glazer
P M
PM
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis / Q000378:metabolism*; D004260:DNA Repair; D005822:Genetic Vectors; D000882:Haplorhini; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009838:Oligodeoxyribonucleotides / Q000378:metabolism*; D017354:Point Mutation; D017384:Sequence Deletion; D014158:Transcription, Genetic; D014162:Transfection
D009838:Oligodeoxyribonucleotides; C051802:triplex DNA; D004247:DNA