The transcription stress response

Abstract

The RNA polymerase II transcription machinery acts as a molecular motor that traverses large parts of the genome on a regular basis. It has been suggested that the transcription machinery may play an important role in sensing DNA damage and activating DNA repair and stress response pathways when stalled at blocking lesions. We have collectively termed the activation of these different pathways as the transcription stress response. Recently, it was shown that the ATR kinase and the single-strand DNA-binding protein RPA mediate the phosphorylation of p53 following blockage of transcription elongation. This ATR-mediated phosphorylation occurs even when transcription elongation is blocked in the absence of DNA damage, suggesting that ATR and RPA senses the consequences of blocked transcription elongation rather than sensing DNA lesions directly. It is proposed that the transcription stress response activated by blockage of transcription may play an important role in safeguarding the genome from DNA damage and thus act to suppress tumorigenesis.