Journal
CELL
Volume 170, Issue 4, Pages 787-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2017.07.044
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Funding
- Cell and Molecular Biology Training Grant [T32 GM 007270]
- National Institutes of Health [AI116669, AI108698]
- Pew Scholars Program in the Biomedical Sciences
- National Institute of Health [DP2GM110773]
- National Science Foundation [MCB1243492]
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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.
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