Transcription Dynamics Prevent RNA-Mediated Genomic Instability

Genomic instability is frequently caused by nucleic acid structures termed R-loops that are formed during transcription. Despite their harmful potential, mechanisms that sense, signal, and suppress these structures remain elusive. We have showed that oscillations in RNA Pol II dynamics during transcription initiate a molecular pathway that prevents R-loops accumulation. Depletion of either SRPK2 or DDX23, as observed in adenoid cystic carcinoma, disrupts this pathway, leading to RNA-mediated genomic instability (Sridhara et al, Cell Reports, 2017).