Transcription remodeling and stalling by cisplatin-induced interstrand crosslinks.

Cisplatin-induced interstrand crosslinks cause RNA polymerase II to remodel the lesion into a novel conformation, stalling transcription and influencing chemotherapy responses.

• Why it matters: Understanding how transcription is blocked by ICLs is crucial because it impacts the effectiveness of platinum-based chemotherapies and cellular repair mechanisms, which are not fully understood.
• What they did: Using reconstituted transcription systems and cryo-electron microscopy, the study captured eight sequential states of Pol II interacting with cisplatin-ICLs, revealing a unique lesion conformation and transcriptional response.
• The result: The findings show Pol II actively remodels ICLs into a conformation that prevents lesion bypass and stalls transcription, highlighting a structural basis for cellular responses to platinum drugs and repair pathways.