Co-orientation of replication and transcription preserves genome integrity.
Abstract
In many bacteria, there is a genome-wide bias towards co-orientation of replication
and transcription, with essential and/or highly-expressed genes further enriched co-directionally.
We previously found that reversing this bias in the bacterium Bacillus subtilis slows
replication elongation, and we proposed that this effect contributes to the evolutionary
pressure selecting the transcription-replication co-orientation bias. This selection
might have been based purely on selection for speedy replication; alternatively, the
slowed replication might actually represent an average of individual replication-disruption
events, each of which is counter-selected independently because genome integrity is
selected. To differentiate these possibilities and define the precise forces driving
this aspect of genome organization, we generated new strains with inversions either
over approximately 1/4 of the chromosome or at ribosomal RNA (rRNA) operons. Applying
mathematical analysis to genomic microarray snapshots, we found that replication rates
vary dramatically within the inverted genome. Replication is moderately impeded throughout
the inverted region, which results in a small but significant competitive disadvantage
in minimal medium. Importantly, replication is strongly obstructed at inverted rRNA
loci in rich medium. This obstruction results in disruption of DNA replication, activation
of DNA damage responses, loss of genome integrity, and cell death. Our results strongly
suggest that preservation of genome integrity drives the evolution of co-orientation
of replication and transcription, a conserved feature of genome organization.
Type
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https://hdl.handle.net/10161/4458Published Version (Please cite this version)
10.1371/journal.pgen.1000810Publication Info
Srivatsan, Anjana; Tehranchi, Ashley; MacAlpine, David M; & Wang, Jue D (2010). Co-orientation of replication and transcription preserves genome integrity. PLoS Genet, 6(1). pp. e1000810. 10.1371/journal.pgen.1000810. Retrieved from https://hdl.handle.net/10161/4458.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
David Michael MacAlpine
Professor of Pharmacology and Cancer Biology
Our laboratory is interested in understanding the mechanisms by which the molecular
architecture of the chromosome regulates fundamental biological processes such as
replication and transcription. Specifically, how are replication, transcription and
chromatin modification coordinated on a genomic scale to maintain genomic stability?
We are addressing this question by using genomic, computational and biochemical approaches
in the model organism Drosophila melanogaster. DNA replica

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