Replication-Transcription Conflicts Generate R-Loops that Orchestrate Bacterial Stress Survival and Pathogenesis

Publication date: 10 August 2017
Source:Cell, Volume 170, Issue 4
Author(s): Kevin S. Lang, Ashley N. Hall, Christopher N. Merrikh, Mark Ragheb, Hannah Tabakh, Alex J. Pollock, Joshua J. Woodward, Julia E. Dreifus, Houra Merrikh
Replication-transcription collisions shape genomes, influence evolution, and promote genetic diseases. Although unclear why, head-on transcription (lagging strand genes) is especially disruptive to replication and promotes genomic instability. Here, we find that head-on collisions promote R-loop formation in Bacillus subtilis. We show that pervasive R-loop formation at head-on collision regions completely blocks replication, elevates mutagenesis, and inhibits gene expression. Accordingly, the activity of the R-loop processing enzyme RNase HIII at collision regions is crucial for stress survival in B. subtilis, as many stress response genes are head-on to replication. Remarkably, without RNase HIII, the ability of the intracellular pathogen Listeria monocytogenes to infect and replicate in hosts is weakened significantly, most likely because many virulence genes are head-on to replication. We conclude that the detrimental effects of head-on collisions stem primarily from excessive R-loop formation and that the resolution of these structures is critical for bacterial stress survival and pathogenesis.

Graphical abstract

Teaser

Head-on replication-transcription collisions lead to pervasive R-loop formation, which must be resolved for bacterial stress survival and pathogenesis.


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