Elf1 promotes Rad26's interaction with lesion- arrested Pol II for transcription- coupled repair

Transcription- coupled nucleotide excision repair (TC- NER) is a highly conserved DNA repair pathway that removes bulky lesions in the transcribed genome. Cockayne syndrome B protein (CSB), or its yeast ortholog Rad26, has been known for dec-ades to play important roles in the lesion- recognition steps of TC- NER. Another conserved protein ELOF1, or its yeast ortholog Elf1, was recently identified as a core transcription- coupled repair factor. How Rad26 distinguishes between RNA polymerase II (Pol II) stalled at a DNA lesion or other obstacles and what role Elf1 plays in this process remains unknown. Here, we present cryo- EM structures of Pol II- Rad26 complexes stalled at different obstacles that show that Rad26 uses a common mechanism to recognize a stalled Pol II, with additional interactions when Pol II is arrested at a lesion. A cryo- EM structure of lesion- arrested Pol II- Rad26 bound to Elf1 revealed that Elf1 induces further interactions between Rad26 and a lesion- arrested Pol II. Biochemical and genetic data support the importance of the interplay between Elf1 and Rad26 in TC- NER initiation. Together, our results provide important mechanistic insights into how two conserved transcription- coupled repair factors, Rad26/CSB and Elf1/ELOF1, work together at the initial lesion recognition steps of transcription- coupled repair.