Mfd - at the crossroads of bacterial DNA repair, transcriptional regulation and molecular evolvability

For survival, bacteria need to continuously evolve and adapt to complex environments, including those that may impact the integrity of the DNA, the repository of genetic information to be passed on to future generations. The multiple factors of DNA repair share the substrate on which they operate with other key cellular machineries, principally those of replication and transcription, implying a high degree of coordination of DNA-based activities. In this review, I focus on progress made in the understanding of the protein factors operating at the crossroads of these three fundamental processes, with emphasis on the mutation frequency decline protein (Mfd, aka TRCF). Although Mfd research has a rich history that goes back in time for more than half a century, recent reports hint that much remains to be uncovered. I argue that besides being a transcription-repair coupling factor (TRCF), Mfd is also a global regulator of transcription and a pro-mutagenic factor, and that the way it interfaces with transcription, replication and nucleotide excision repair makes it an attractive candidate for the development of strategies to curb molecular evolution, hence, antibiotic resistance.