Bypass of Blocking Lesions by RNAPII Impairs the Transcriptional DNA Damage Response.

Ultraviolet (UV) irradiation and platinum-based drugs generate bulky DNA lesions that impede transcription elongation by RNA Polymerase II (RNAPII). This transcriptional block triggers a coordinated stress response involving transcription-coupled nucleotide excision repair (TC-NER), removal and degradation of the stalled RNAPII, and global transcriptional shutdown. However, the molecular and cellular consequences of RNAPII bypassing such lesions remain unclear.