Head-on replication-transcription collisions lead to formation of life threatening R-loops
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TLDR
It is concluded 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.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.read more
Citations
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Ordered association of helicase loader proteins with the Bacillus subtilis origin of replication in vivo
TL;DR: In this article, the essential proteins DnaB, DnaD and DnaI of Bacillus subtilis are required for initiation, but not elongation, of DNA replication and for replication restart at stalled forks.
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TL;DR: The factors and cellular processes that control R loop formation and the mechanisms by which R loops may influence gene expression and the integrity of the genome are discussed.
Journal ArticleDOI
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