Transcription in check at DNA double-strand breaks

When DNA double-strand breaks (DSBs) arise within actively transcribed loci, cells must tightly coordinate transcription with DNA repair to avoid detrimental interference between these processes. This coordination is initiated by signaling cascades that rapidly repress local transcription through chromatin remodeling, recruitment of repressive factors, and modifications of RNA polymerase II (RNAPII). However, the mechanisms that orchestrate and integrate these events remain incompletely understood. In this review, we discuss recent advances in the field and draw parallels with the pathways handling transcription-blocking lesions, such as those caused by UV irradiation or DNA-protein crosslinks. We further discuss the possibility that an altered transcription cycle, marked by slowed or stalled RNAPII, drives the production of distinct RNA species at DSB sites, thereby reconciling previously conflicting observations.