Mutation Frequency Decline

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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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