Mfd Dynamically Regulates Transcription

Fundamental processes that occur along DNA, such as transcription and replication, commonly encounter obstacles or 'roadblocks' which may impede progress and ultimately result in mutations and/or DNA damage. Thus, spatiotemporal control of these factors can have far-reaching consequences. In bacteria, the mutation frequency decline (Mfd) protein has been widely recognized for dealing with transcriptional roadblock resolution through either facilitating transcription through a roadblock or terminating transcription altogether. Despite this importance, it is unclear how Mfd interacts with RNAP and DNA and how such interactions lead to obstacle resolution. Using novel assays, we discovered that Mfd interacts with RNAP in a dynamic and highly regulated fashion. Our findings demonstrate a remarkably delicate coordination between Mfd and RNAP, allowing efficient targeting and recycling of Mfd, and expedient conflict resolution.