Biology subjects

Hall, A. N.

Publications and source records attributed to Hall, A. N..

2 recordsLinked to original sources

bioRxiv2017

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

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.

molecular biology↗

bioRxiv2017

Short tandem repeats with massive variation and functional consequences across strains of Arabidopsis thaliana

Short tandem repeat (STR) mutations may be responsible for more than half of the mutations in eukaryotic coding DNA, yet STR variation is rarely examined as a contributor to complex traits. We assess the scope of this contribution across a collection of 96 strains of Arabidopsis thaliana by massively parallel STR genotyping. We found that 95% of examined STRs are polymorphic, with a median of six alleles per STR in these strains. Modest STR expansions are found in most strains, some of which have evident functional effects. For instance, three of six intronic STR expansions are associated with intron retention. Coding STRs are depleted of variation relative to non-coding STRs, consistent with the action of purifying selection, and some STRs show hypervariable patterns consistent with diversifying selection. Finally, we detect dozens of novel STR-phenotype associations that could not be detected with SNPs alone, validating several with follow-up experiments. Our results demonstrate that STRs comprise a large, unascertained reservoir of functionally relevant genomic variation.

genomics↗