The enigmatic role of Mfd in replication-transcription conflicts in bacteria

Conflicts between replication and transcription can have life-threatening consequences. RNA polymerase (RNAP) is the major impediment to replication progression, and its efficient removal from DNA should mitigate the consequences of collisions with replication. Cells have various proteins that can resolve conflicts by removing stalled (or actively translocating) RNAP from DNA. It would therefore seem logical that RNAP-associated factors, such as the bacterial DNA translocase Mfd, would minimize the effects of conflicts. Despite seemingly conclusive statements in most textbooks, the role of Mfd in conflicts remains an enigma. In this review, we will discuss the different physical states of RNAP during transcription, and how each distinct state can influence conflict severity and potentially trigger the involvement of Mfd. We propose models to explain the contradictory conclusions from published studies on the potential role of Mfd in resolving conflicts.