Phenotypic change caused by transcriptional bypass of uracil in nondividing cells.
Cytosine deamination to uracil occurs frequently in cellular DNA. In vitro, RNA polymerase efficiently inserts adenine opposite to uracil, resulting in G to A base substitutions. In vivo, uracil could potentially alter transcriptional fidelity, resulting in production of mutant proteins. This study demonstrates that in nondividing Escherichia coli cells, a DNA template base replaced with uracil in a stop codon in the firefly luciferase gene results in conversion of inactive to active luciferase. The level of transcriptional base substitution is dependent on the capacity to repair uracil. These results provide evidence for a DNA damage-dependent, transcription-driven pathway for generating mutant proteins in nondividing cells.
Viswanathan
A
A
Graduate Program in Genetics and Molecular Biology and Departments of Biochemistry and Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA.
You
H J
HJ
Doetsch
P W
PW
D020137:Base Pair Mismatch; D018388:Codon, Terminator; D004249:DNA Damage; D004260:DNA Repair; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D017930:Genes, Reporter; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D016296:Mutagenesis; D009675:Novobiocin / Q000494:pharmacology; D010641:Phenotype; D014176:Protein Biosynthesis; D012329:RNA, Bacterial / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D013698:Templates, Genetic; D014158:Transcription, Genetic; D014498:Uracil / Q000378:metabolism*
D018388:Codon, Terminator; D004269:DNA, Bacterial; D012329:RNA, Bacterial; D012333:RNA, Messenger; D009675:Novobiocin; D014498:Uracil; D008156:Luciferases; D012321:DNA-Directed RNA Polymerases