The Transcription-Repair Coupling Factor Mfd Prevents and Promotes Mutagenesis in a Context-Dependent Manner

• Published in: Frontiers in molecular biosciences Vol. 8; p. 668290
• Main Authors: Lindsey-Boltz, Laura A, Sancar, Aziz
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 20.05.2021
• Subjects: excision repair-sequencing (XR-seq); Molecular Biosciences; mutation frequency decline (MFD); nucleotide excision repair (NER); transcription-coupled repair (TCR); uvrABC excinuclease; UvrD; uvrABC excinuclease; UvrD; excision repair-sequencing (XR-seq); nucleotide excision repair (NER); transcription-coupled repair (TCR); mutation frequency decline (MFD)
• ISSN: 2296-889X; 2296-889X
• DOI: 10.3389/fmolb.2021.668290

The (mutation frequency decline) gene was identified by screening an auxotrophic strain exposed to UV and held in a minimal medium before plating onto rich or minimal agar plates. It was found that, under these conditions, holding cells in minimal (nongrowth) conditions resulted in mutations that enabled cells to grow on minimal media. Using this observation as a starting point, a mutant was isolated that failed to mutate to auxotrophy under the prescribed conditions, and the gene responsible for this phenomenon (mutation frequency decline) was named . Later work revealed that encoded a translocase that recognizes a stalled RNA polymerase (RNAP) at damage sites and binds to the stalled RNAP, recruits the nucleotide excision repair damage recognition complex UvrA UvrB to the site, and facilitates damage recognition and repair while dissociating the stalled RNAP from the DNA along with the truncated RNA. Recent single-molecule and genome-wide repair studies have revealed time-resolved features and structural aspects of this transcription-coupled repair (TCR) phenomenon. Interestingly, recent work has shown that in certain bacterial species, also plays roles in recombination, bacterial virulence, and the development of drug resistance.