Genome-wide strand-specific UV mutagenesis in <i> <i>Escherichia coli</i> </i> is directed by the Mfd translocase

Transcription-coupled repair in <i><i>Escherichia coli</i></i> which is mediated by the Mfd translocase is responsible for higher repair rate in <i>lacZ</i> and <i>lacI</i> genes upon induction of transcription. Here, we analyze the entire <i><i>E. coli</i></i> genome for the effect of Mfd on UV-induced mutagenesis. We find genome-wide preferential repair of the transcribed strand (TS) over the nontranscribed strand (NTS), and consequently, fewer mutations are caused by cyclobutane pyrimidine dimers in the TS than the NTS, in a manner proportional to transcription rate. In <i>mfd-</i> cells, most mutations are in the TS, caused by RNA polymerase stalled at template strand damage inhibiting repair. These findings are pertinent to <i>mfd</i>^- phenotypes involving gene expression, recombination, stationary phase mutagenesis, and drug resistance.