During gene transcription, RNA polymerase (Pol) II encounters obstacles, including lesions in the DNA template. Here, we review a recent structure–function analysis of Pol II transcribing DNA with a bulky photo-lesion in the template strand. The study provided the molecular basis for recognition of a damaged DNA by Pol II, which is the first step in transcription- coupled DNA repair (TCR). The results have general implications for damage recognition and the TCR mechanism.