title: Increased transcription decreases the spontaneous mutation rate at the thymidine kinase locus in human cells.
abstract: Transcription increases DNA repair efficiency and modulates the distribution of certain types of DNA damage. Furthermore, increased transcription level stimulates spontaneous mutation rate in yeast. We explored whether transcription level affects spontaneous mutation rate in human cells. We first developed two thymidine kinase (tk) inducible human cell lines using the Gal4-Estrogen receptor system. In our TK6i-G3 and G9 tk heterozygous cell lines, the active tk allele is linked to an inducible promoter element. Tk mRNA is induced following treatment with estrogen. Spontaneous mutation rate was significantly decreased in human cell lines after induction in contrast to the report in yeast. Thus, humans may have evolved different or additional mechanisms to deal with transcription related spontaneous mutagenesis.
authors.affiliation: Department of Cancer Biology, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Lippert
authors.forename: Q
authors.initials: Q
authors.lastname: Chen
authors.forename: H L
authors.initials: HL
authors.lastname: Liber
mesh_terms: D001402:B-Lymphocytes; D002460:Cell Line; D004260:DNA Repair; D004268:DNA-Binding Proteins; D018274:Electroporation; D004790:Enzyme Induction; D004958:Estradiol / Q000494:pharmacology; D005656:Fungal Proteins / Q000096:biosynthesis; D006579:Heterozygote; D006801:Humans; D007700:Kinetics; D009154:Mutation; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D029701:Saccharomyces cerevisiae Proteins; D013937:Thymidine Kinase / Q000096:biosynthesis / Q000235:genetics*; D013997:Time Factors; D015534:Trans-Activators / Q000096:biosynthesis; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D004958:Estradiol; D013937:Thymidine Kinase