Transcription remodeling and stalling by cisplatin-induced interstrand crosslinks.

Pol II remodels cisplatin-induced interstrand crosslinks into a novel conformation that stalls transcription, with eight sequential states captured by cryo-EM.

• Why it matters: Understanding how ICLs block transcription is crucial for improving platinum-based chemotherapy, as current repair mechanisms can mitigate drug efficacy.
• What they did: Using reconstituted transcription systems and cryo-electron microscopy, the study examined Pol II processing of cisplatin-ICLs, revealing a structural remodeling of the lesion and eight transcriptional states.
• The result: Pol II's remodeling prevents lesion entry into the active site and causes backtracking, while Cockayne syndrome protein B does not promote bypass or displace stalled Pol II, informing cellular responses to chemotherapy.