Mutation Frequency Decline

Mutation Frequency Decline (mfd) is the gene which encodes the protein Mfd (also known as Transcription Repair Coupling Factor (TRCF)). Mfd functions in transcription-coupled repair to remove a stalled RNA polymerase that has encountered DNA damage and is unable to continue translocating. Mfd utilizes ATP to translocate along DNA, most likely forcing RNA polymerase forward and ultimately dissociating it from the DNA template (Roberts & Park, Current Opinion in Microbiology 2004, DOI 10.1016/j.mib2004.02.014). Mfd also contains binding domains which recruit UvrA and trigger the associated nucleotide excision repair pathway and was initially discovered when its mutation led to a decrease in mutation rates after irradiation by UV light. Structural studies of E. coli Mfd by X-ray crystallography have revealed that this molecule is autoinhibited for UvrA-binding in its apo form due to a "clamp" interaction between the N-terminal UvrB-homology module and the C-terminal domain [Deaconescu et al. Trends Biochem Sci. 2012 (12):543-52; Cell. 2006 124(3):507-20].

It has been shown that Mfd may also re-initiate transcription at backtracked RNAP by forcing the polymerase forward and out of its backtracked state (Park, Marr & Roberts, Cell vol 109 June 14, 2002 PMID 12086674).