The Cellular Response to Transcription-Blocking DNA Damage. Issue 5 (May 2018) - Gregersen, Lea H.
Abstract : In response to transcription-blocking DNA lesions such as those generated by UV irradiation, cells activate a multipronged DNA damage response. This response encompasses repair of the lesions that stall RNA polymerase (RNAP) but also a poorly understood, genome-wide shutdown of transcription, even of genes that are not damaged. Over the past few years, a number of new results have shed light on this intriguing DNA damage response at the structural, biochemical, cell biological, and systems biology level. In this review we summarize the most important findings. Highlights: Biochemical and genetic studies indicate crosstalk between TC-NER factors and factors regulating RNAPII backtracking and elongation. TC-NER is controlled by an unexpectedly complex layer of post-translational regulation targeting repair factors and RNAPII itself. Dramatic changes to the transcriptional program in response to UV irradiation have been revealed by high-throughput genome-wide and time-resolved measurements. Chromatin remodelers, splicing factors, noncoding RNAs, and RNA modifications provide a multifaceted transcriptional response to UV irradiation.