HOME

TheInfoList



Click Here for Items Related To - Mutation Frequency Decline
OR:
Mutation Frequency Decline on:   [Wikipedia]   [Google]   [Amazon]

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 In molecular biology, RNA polymerase (abbreviated RNAP or RNApol), or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that synthesizes RNA from a DNA template. Using the enzyme helicase, RNAP locally opens the ...
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 UvrABC endonuclease is a multienzyme complex in bacteria involved in DNA repair by nucleotide excision repair, and it is, therefore, sometimes called an excinuclease. This UvrABC repair process, sometimes called the short-patch process, involve ...
and trigger the associated
nucleotide excision repair Nucleotide excision repair is a DNA repair mechanism. DNA damage occurs constantly because of chemicals (e.g. intercalating agents), radiation and other mutagens. Three excision repair pathways exist to repair single stranded DNA damage: Nucle ...
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 ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...
'' 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 The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...
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 Seattle a ...
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 Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. All classes of microbes can evolve resistance. Fungi evolve antifungal resistance. Viruses evolve antiviral resistance. ...
.


References

Mutation {{molecular-biology-stub