title: Mfd Protein and Transcription-Repair Coupling in Escherichia coli.
abstract: In 1989, transcription-repair coupling (TRC) was first described in Escherichia coli, as the transcription-dependent, preferential nucleotide excision repair (NER) of UV photoproducts located in the template DNA strand. This finding led to pioneering biochemical studies of TRC in the laboratory of Professor Aziz Sancar, where, at the time, major contributions were being made toward understanding the roles of the UvrA, UvrB and UvrC proteins in NER. When the repair studies were extended to TRC, template but not coding strand lesions were found to block RNA polymerase (RNAP) in vitro, and unexpectedly, the blocked RNAP inhibited NER. A transcription-repair coupling factor, also called Mfd protein, was found to remove the blocked RNAP, deliver the repair enzyme to the lesion and thereby mediate more rapid repair of the transcription-blocking lesion compared with lesions elsewhere. Structural and functional analyses of Mfd protein revealed helicase motifs responsible for ATP hydrolysis and DNA binding, and regions that interact with RNAP and UvrA. These and additional studies provided a basis upon which other investigators, in following decades, have characterized fascinating and unexpected structural and mechanistic features of Mfd, revealed the possible existence of additional pathways of TRC and discovered additional roles of Mfd in the cell.
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Selby
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000378:metabolism; D006868:Hydrolysis; D008954:Models, Biological; D011487:Protein Conformation; D013698:Templates, Genetic; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic; D014466:Ultraviolet Rays
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D014157:Transcription Factors; C072103:transcription repair coupling factor protein, Bacteria; D000255:Adenosine Triphosphate; D012321:DNA-Directed RNA Polymerases