Show simple item record Srivatsan, A Tehranchi, A MacAlpine, DM Wang, JD
dc.coverage.spatial United States 2011-06-21T17:31:15Z 2010-01-15
dc.identifier.citation PLoS Genet, 2010, 6 (1), pp. e1000810 - ?
dc.description.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.
dc.format.extent e1000810 - ?
dc.language ENG
dc.language.iso en_US en_US
dc.relation.ispartof PLoS Genet
dc.relation.isversionof 10.1371/journal.pgen.1000810
dc.subject Bacillus subtilis
dc.subject DNA Replication
dc.subject Genome, Bacterial
dc.subject Mutation
dc.subject Transcription, Genetic
dc.title Co-orientation of replication and transcription preserves genome integrity.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US 2010-1-0 en_US
duke.description.endpage e1000810 en_US
duke.description.issue 1 en_US
duke.description.startpage e1000810 en_US
duke.description.volume 6 en_US
dc.relation.journal Plos Genetics en_US
pubs.issue 1
pubs.organisational-group /Duke
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Pharmacology & Cancer Biology
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Cancer Institute
pubs.publication-status Published online
pubs.volume 6
dc.identifier.eissn 1553-7404

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