DNA polymerase bypass in vitro and in E. coli of a C-nucleotide analogue of Fapy·dG

• Published in: Bioorganic & medicinal chemistry 2008-04, Vol.16 (7), p.4029-4034
• Main Authors: Weledji, Yvonne N., Wiederholt, Carissa J., Delaney, Michael O., Greenberg, Marc M.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; DNA damage; DNA lesions; DNA Polymerase I - metabolism; DNA replication; Escherichia coli - drug effects; Escherichia coli - enzymology; Escherichia coli - genetics; Formamides - chemical synthesis; Formamides - chemistry; Formamides - pharmacology; Fundamental and applied biological sciences. Psychology; Furans - chemical synthesis; Furans - chemistry; Furans - pharmacology; Genome, Bacterial - genetics; Kinetics; Modified nucleotides; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Molecular Structure; Mutagenesis. Repair; Nucleotides - chemistry; Pyrimidines - chemical synthesis; Pyrimidines - chemistry; Pyrimidines - pharmacology
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2008.01.025

β-C-Fapy·dG is an analogue of Fapy·dG that is stable to repair. DNA polymerase bypass of β-C-Fapy·dG in Escherichia coli indicates that it is not mutagenic. β-C-Fapy·dG could be useful as a DNA repair inhibitor. Bypass of the configurationally stable analogue (β-C-Fapy·dG) of the formamidopyrimidine lesion derived from 2′-deoxyguanosine oxidation (Fapy·dG) was studied in vitro and in Escherichia coli. The exonuclease deficient Klenow fragment of E. coli DNA polymerase I (Klenow exo −) misincorporated dA most frequently opposite β-C-Fapy·dG, but its efficiency was