INCREASED TRANSCRIPTION DECREASES THE SPONTANEOUS MUTATION-RATE AT THE THYMIDINE KINASE LOCUS IN HUMAN-CELLS

Transcription increases DNA repair efficiency and modulates the distri bution of certain types of DNA damage. Furthermore, increased transcri ption level stimulates spontaneous mutation rate in yeast. We explored whether transcription level affects spontaneous mutation rate in huma n cells. Pie first developed two thymidine kinase (tk) inducible human cell lines using the Gal4-Estrogen receptor system. In our TK6i-G3 an d G9 tk heterozygous cell lines, the active tk allele is linked to an inducible promoter element. Tk mRNA is induced following treatment wit h estrogen. Spontaneous mutation rate was significantly decreased in h uman cell lines after induction in contrast to the report in yeast. Th us, humans may have evolved different or additional mechanisms to deal with transcription related spontaneous mutagenesis. (C) 1998 Elsevier Science B.V. All rights reserved.