Marjolein van Sluis, Qing Yu, Melanie van der Woude, Camila Gonzalo-Hansen, Shannon C Dealy, Roel C Janssens, Hedda B Somsen, Anisha R Ramadhin, Dick H W Dekkers, Hannah Lena Wienecke, Joris J P G Demmers, Anja Raams, Carlota Davó-Martínez, Diana A Llerena Schiffmacher, Marvin van Toorn, David Häckes, Karen L Thijssen, Di Zhou, Judith G Lammers, Alex Pines, Wim Vermeulen, Joris Pothof, Jeroen A A Demmers, Debbie L C van den Berg, Hannes Lans, Jurgen A Marteijn
DNA-protein crosslinks (DPCs) arise from enzymatic intermediates, metabolism or chemicals like chemotherapeutics. DPCs are highly cytotoxic as they impede DNA-based processes such as replication, which is counteracted through proteolysis-mediated DPC removal by spartan (SPRTN) or the proteasome. However, whether DPCs affect transcription and how transcription-blocking DPCs are repaired remains largely unknown. Here we show that DPCs severely impede RNA polymerase II-mediated transcription and are preferentially repaired in active genes by transcription-coupled DPC (TC-DPC) repair...
April 10, 2024: Nature Cell Biology