The molecular mechanism of transcription-coupled DNA repair.

DNA damage that blocks the transcription of genes is prioritized for repair by transcription-coupled DNA repair pathways. RNA polymerases stalled at DNA lesions obstruct repair enzymes, but this situation is turned to the advantage of the cell by transcription-repair coupling factors that remove the stalled RNA polymerase from DNA and increase the rate at which the lesion is repaired. Recent structural studies of the bacterial transcription-repair coupling factor, Mfd, have revealed a modular architecture in which an ATP-dependent DNA-based motor is coupled to protein-protein interaction domains that can attach the motor to RNA polymerase and the DNA repair protein UvrA. Here I review the key features of this multifunctional protein and discuss how recent mechanistic and structural findings have advanced our understanding of transcription-coupled DNA repair in bacteria.