Comparison of ultraviolet irradiation-induced mutagenesis of the lacI gene in Escherichia coli and in human 293 cells

• Published in: Journal of molecular biology Vol. 205; no. 1; pp. 103 - 113
• Main Authors: Hsia, Han Chao, Lebkowski, Jane S, Leong, Phaik-Mooi, Calos, Michele P, Miller, Jeffrey H
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 05.01.1989; Elsevier
• Subjects: Base Sequence; Biological and medical sciences; Cells, Cultured; Dose-Response Relationship, Radiation; Escherichia coli; Escherichia coli - genetics; Fundamental and applied biological sciences. Psychology; Genes, Bacterial; Genes, Regulator; Humans; Lactose - genetics; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Mutagenesis. Repair; Mutation; Transfection; Ultraviolet Rays; u.v; X-gal; Human; Cell culture; Ultraviolet radiation; Mutagenesis; Escherichia coli; Bacteria; Escherichieae; Enterobacteriaceae
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/0022-2836(89)90368-9

We report the sequence changes in the Escherichia coli lacI gene in 133 mutants detected after passage of an ultraviolet-irradiated shuttle vector human 293 cells. The results are compared with our previous studies of the lacI gene after ultraviolet light treatment in E. coli. In human cells, base substitutions predominate, and frameshifts are found much less frequently than in bacteria. The most frequent base change is the G·C to A·T transition. Overall. 110 of 112 transitions were G·C to A·T. Some of the hotspots seen in lacI in bacteria are prominent also in human 293 cells, suggesting that the same lesions are targeting mutations in both systems. Transitions are found almost exclusively at sequences at which pyrimidine-pyrimidine photoproducts can form. The data are consistent with the notion that a significant fraction of ultraviolet irradiation-induced mutagenesis in mammalian systems occurs by adding an A across from a photolesion. Double mutations are significantly more frequent in human cells than in bacteria. Reasons for this difference are discussed.