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.

About

Mfd utilizes ATP to translocate along DNA, most likely forcing RNA polymerase forward and ultimately dissociating it from the DNA template.[1] 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.[2][3]

In 2002, it was shown that Mfd may also re-initiate transcription at backtracked RNAP by forcing the polymerase forward and out of its backtracked state.[4]

In 2015, Merrikh Lab at University of Washington discovered the bacterial protein called Mutation Frequency Decline (Mfd) quickens the bacterial mutation process.[5] This work researches ways to slow the rate of bacterial mutations and to block their evolution, in order to fight against antibiotic resistance.[6]

References
  1. Roberts, Jeffrey; Park, Joo-Seop (2004). "Mfd, the bacterial transcription repair coupling factor: translocation, repair and termination". Current Opinion in Microbiology. 7 (2): 120–125. doi:10.1016/j.mib.2004.02.014. PMID 15063847.
  2. Deaconescu, Alexandra M.; Artsimovitch, Irina; Grigorieff, Nikolaus (December 2012). "Interplay of DNA repair with transcription: from structures to mechanisms". Trends in Biochemical Sciences. 37 (12): 543–552. doi:10.1016/j.tibs.2012.09.002. ISSN 0968-0004. PMC 3588851. PMID 23084398.
  3. Deaconescu, Alexandra M.; Chambers, Anna L.; Smith, Abigail J.; Nickels, Bryce E.; Hochschild, Ann; Savery, Nigel J.; Darst, Seth A. (2006). "Structural Basis for Bacterial Transcription-Coupled DNA Repair". Cell. 124 (3): 507–520. doi:10.1016/j.cell.2005.11.045. PMID 16469698.
  4. Park, Joo-Seop; Marr, Michael T.; Roberts, Jeffrey W. (2002-06-14). "E. coli Transcription repair coupling factor (Mfd protein) rescues arrested complexes by promoting forward translocation". Cell. 109 (6): 757–767. doi:10.1016/s0092-8674(02)00769-9. ISSN 0092-8674. PMID 12086674.
  5. Palisoc, Mhean (2019-01-03). "Merrikh Lab Working to Defeat Drug-Resistant Superbugs". Science and Technology Research News. Retrieved 2019-10-22.
  6. "Il y a peut-être une solution pour stopper la résistance aux antibiotiques". Slate.fr (in French). 2018-12-31. Retrieved 2019-10-22.


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