RECQL5 and transcription-coupled DNA repair complex coordinate to regulate transcription elongation

The RECQL5 helicase is crucial for maintaining genome stability and functions at the intersection of transcription, replication, and DNA repair. RECQL5 associates with RNA15 polymerase II (Pol II) to modulate transcription elongation, yet the underlying mechanism remains unclear. Here, we report cryo-electron microscopy structures of human RECQL5 bound to multiple transcription elongation complexes. Combined with biochemical analysis, we identified an a-helix of RECQL5 responsible for Pol II binding and inhibition of transcription elongation. We further reveal that the transcription-coupled DNA repair (TCR) complex20 reactivates the transcription of RECQL5-inhibited Pol II through concerted actions of its translocase activity and competition with the RECQL5 helix for engaging Pol II. Our results suggest a model in which RECQL5 and TCR coordinately regulate the transcription elongation rate to ensure transcription efficiency while maintaining genome stability.