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bioRxiv · 10.1101/154427

Head-on replication-transcription collisions lead to formation of life threatening R-loops

Lang, K. S.·Hall, A. N.·Merrikh, C. N.·Ragheb, M.·Merrikh, H.
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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.

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Lang, K. S., Hall, A. N., Merrikh, C. N., Ragheb, M., Merrikh, H.. 2017-06-23. Head-on replication-transcription collisions lead to formation of life threatening R-loops. https://doi.org/10.1101/154427

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