Transcriptional mutagenesis induced by uracil and 8-oxoguanine in Escherichia coli.
Cells exposed to DNA damaging agents in their natural environment do not undergo continuous cycles of replication but are more frequently engaged in gene transcription. Luciferase gene expression analysis with DNA templates containing uracil or 8-oxoguanine, placed at a defined position, indicated that in nondividing Escherichia coli cells, efficient mutagenic lesion bypass does occur in vivo during transcription. Sequence analyses of the transcript population revealed that RNA polymerase inserts adenine opposite to uracil, and adenine or cytosine opposite to 8-oxoguanine. Surprisingly, deletions were also detected for 8-oxoguanine-containing templates, indicating RNA polymerase slippage over this lesion. Genetic analyses showed that, in E. coli, 8-oxoguanine is subject to transcription-coupled repair. Consequently, DNA damages alter transcription fidelity in vivo, which may lead to the production of mutant proteins that have the potential to change the phenotype of nondividing cells.
Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
Damien
D
Brégeon
Zara A
ZA
Doddridge
Ho Jin
HJ
You
Bernard
B
Weiss
Paul W
PW
Doetsch
D001483:Base Sequence / Q000187:drug effects / Q000235:genetics; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000096:biosynthesis / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects / Q000235:genetics; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D016296:Mutagenesis / Q000187:drug effects / Q000235:genetics*; D010641:Phenotype; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics*; D014498:Uracil / Q000378:metabolism / Q000494:pharmacology*
D029968:Escherichia coli Proteins; C024829:8-hydroxyguanine; D014498:Uracil; D006147:Guanine; D012321:DNA-Directed RNA Polymerases