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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. 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 X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...
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 The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
domain. 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. In 2015, Merrikh Lab at
University of Washington The University of Washington (UW, simply Washington, or informally U-Dub) is a public research university in Seattle, Washington. Founded in 1861, Washington is one of the oldest universities on the West Coast; it was established in Seattl ...
discovered the bacterial protein called Mutation Frequency Decline (Mfd) quickens the bacterial mutation process. This work researches ways to slow the rate of bacterial mutations and to block their evolution, in order to fight against antibiotic resistance.


References

Mutation {{molecular-biology-stub