RNA Processing and Genome Stability: Cause and Consequence

It is emerging that the pathways that process newly transcribed RNA molecules also regulate the response to DNA damage at multiple levels. Here, we discuss recent insights into how RNA processing pathways participate in DNA damage recognition, signaling, and repair, selectively influence the expression of genome-stabilizing proteins, and resolve deleterious DNA/RNA hybrids (R-loops) formed during transcription and RNA processing. The importance of these pathways for the DNA damage response (DDR) is underscored by the growing appreciation that defects in these regulatory connections may be connected to the genome instability involved in several human diseases, including cancer. Wickramasinghe and Venkitaraman formulate a conceptual framework for the emerging connections between pathways for RNA processing and DNA damage responses in human cells, exposed in several recent papers. Defects in these connections may provoke genome instability associated with human diseases like cancer.