The faithful transcription of eukaryotic genes by RNA polymerase II (RNAP2) is crucial for proper cell function and tissue homeostasis. However, transcription-blocking DNA lesions of both endogenous and environmental origin continuously challenge the progression of elongating RNAP2. The stalling of RNAP2 on a transcription-blocking lesion triggers a series of highly regulated events, including RNAP2 processing to make the lesion accessible for DNA repair, R-loop-mediated DNA damage signaling, and the initiation of transcription-coupled DNA repair. The correct execution and coordination of these processes is vital for resuming transcription following the successful repair of transcription-blocking lesions. Here, we outline recent insights into the molecular consequences of RNAP2 stalling on transcription-blocking DNA lesions and how these lesions are resolved to restore mRNA synthesis.

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Keywords DNA damage, Nucleotide excision repair, RNA polymerase 2, Transcription coupled repair, Transcription restart
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Journal Journal of Molecular Biology
Steurer, B, & Marteijn, J.A. (2016). Traveling Rocky Roads: The Consequences of Transcription-Blocking DNA Lesions on RNA Polymerase II. Journal of Molecular Biology. doi:10.1016/j.jmb.2016.11.006