@article {Lang154427, author = {Kevin S. Lang and Ashley N. Hall and Christopher N. Merrikh and Mark Ragheb and Houra Merrikh}, title = {Head-on replication-transcription collisions lead to formation of life threatening R-loops}, elocation-id = {154427}, year = {2017}, doi = {10.1101/154427}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Encounters between transcription and DNA replication machineries lead to conflicts that shape genomes, influence evolution, and lead to genetic diseases in humans. Although unclear why, head-on transcription (lagging strand genes) is especially disruptive to replication, increases DNA breaks, and promotes mutagenesis. Here, we show that head-on replication-transcription conflicts lead to pervasive RNA:DNA hybrid formation in Bacillus subtilis. We find that replication beyond head-on conflict regions requires the activity of a RNA:DNA hybrid processing enzyme, RNase HIII. Remarkably, pervasive RNA:DNA hybrid formation at head-on genes completely stops replication and inhibits gene expression in a replication-dependent manner. Accordingly, we find that resolution of head-on conflicts by RNase HIII is crucial for survival upon exposure to various stresses, as many stress response genes are encoded head-on to replication. We conclude that R-loops, RNA:DNA hybrids formed outside of the transcription bubble, exacerbate head-on replication-transcription conflicts, thereby threatening life, especially upon exposure to environmental stresses.}, URL = {https://www.biorxiv.org/content/early/2017/06/23/154427}, eprint = {https://www.biorxiv.org/content/early/2017/06/23/154427.full.pdf}, journal = {bioRxiv} }