Structural investigation of DNA lesion sensing mechanism of UvrA

The nucleotide excision repair (NER) pathway is a universal DNA repair system that removes a broad spectrum of bulky lesions caused by ultraviolet light and chemical agents. A central player in this pathway is UvrA, an ATP-binding cassette (ABC) protein that functions as a dimeric multidomain ATPase. UvrA acts as the primary sensor of DNA damage, scanning the genome and detecting local distortions in the DNA helix. Through cycles of ATP binding and hydrolysis, UvrA undergoes conformational changes that enable it to distinguish damaged from undamaged DNA, recruit UvrB, and trigger the subsequent steps of repair. Despite its essential role in genome maintenance, the structural mechanisms underlying UvrA’s lesion recognition and its dynamic conformational cycle remain only partially understood. Structural investigation of UvrA is therefore crucial to uncover how bacteria detect and process DNA damage, and to provide fundamental insight into the molecular principles of genome surveillance.