From Mfd to TRCF and Back Again-A Perspective on Bacterial Transcription-coupled Nucleotide Excision Repair

Photochemical and other reactions on DNA cause damage and corrupt genetic information. To counteract this damage, organisms have evolved intricate repair mechanisms that often crosstalk with other DNA-based processes such as transcription. Intriguing observations in the late 1980s and early 1990s led to the discovery of transcription-coupled repair (TCR), a subpathway of nucleotide excision repair. TCR, found in all domains of life, prioritizes for repair lesions located in the transcribed DNA strand, directly read by RNA polymerase. Here, we give a historical overview of developments in the field of bacterial TCR, starting from the pioneering work of Evelyn Witkin and Aziz Sancar, which led to the identification of the first transcription-repair coupling factor (the Mfd protein), to recent studies that have uncovered alternative TCR pathways and regulators.