Traffic light at DSB-transit regulation between gene transcription and DNA repair.

Transcription of actively expressed genes is dampened for kilobases around DNA lesions via chromatin modifications. This is believed to favour repair and prevent genome instability. Nonetheless, mounting evidence suggests that transcription may be induced by DNA breakage, resulting in the local de novo synthesis of non-coding RNAs (ncRNAs). Such transcripts have been proposed to play important functions in both DNA damage signalling and repair. Here, we review the recently identified mechanistic details of transcriptional silencing at damaged chromatin, highlighting how post-translational histone modifications can also be modulated by the local synthesis of DNA damage-induced ncRNAs. Finally, we envision that these entangled transcriptional events at DNA breakages can be targeted to modulate DNA repair, with potential implications for locus-specific therapeutic strategies.