The Hardwired Transcriptional Response to DNA Damage

Abstract There is a complex network of interactions between bulky DNA damages and transcription. Bulky damages block RNA polymerases but also elicit a regulated transcriptional response. At the same time, active transcription enhances the ability to recognize and repair damages. Eventually, transcription is completely shut down until after damages are removed. Recent projects untangle this web of interaction in mammalian cells by applying time-sensitive and high-resolution measurements of damage, repair, and transcription at genome-wide scales. The emerging model indicates the transcriptional response to damage is primarily hardwired in the damaged genomic DNA, and transcription shutdown can be explained almost completely by (1) aborted transcription by blocked RNA polymerases and (2) ubiquitination and degradation of RNA polymerase II after encountering a damage.