Reprogramming transcription after DNA damage: recognition, response, repair, and restart

Genome integrity is constantly challenged by endogenous and exogenous insults that cause DNA damage. To cope with these threats, cells have a surveillance mechanism, known as the DNA damage response (DDR), to repair any lesions. Although transcription has long been implicated in DNA repair, how transcriptional reprogramming is coordinated with the DDR is just beginning to be understood. In this review, we highlight recent advances in elucidating the molecular mechanisms underlying major transcriptional events, including RNA polymerase (Pol) II stalling and transcriptional silencing and recovery, which occur in response to DNA damage. Furthermore, we discuss how such transcriptional adaptation contributes to sensing and eliminating damaged DNA and how it can jeopardize genome integrity when it goes awry.