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Co-orientation of replication and transcription preserves genome integrity.

Publication ,  Journal Article
Srivatsan, A; Tehranchi, A; MacAlpine, DM; Wang, JD
Published in: PLoS Genet
January 15, 2010

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.

Duke Scholars

Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

January 15, 2010

Volume

6

Issue

1

Start / End Page

e1000810

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Mutation
  • Genome, Bacterial
  • Developmental Biology
  • DNA Replication
  • Bacillus subtilis
  • 3105 Genetics
  • 0604 Genetics
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Srivatsan, A., Tehranchi, A., MacAlpine, D. M., & Wang, J. D. (2010). Co-orientation of replication and transcription preserves genome integrity. PLoS Genet, 6(1), e1000810. https://doi.org/10.1371/journal.pgen.1000810
Srivatsan, Anjana, Ashley Tehranchi, David M. MacAlpine, and Jue D. Wang. “Co-orientation of replication and transcription preserves genome integrity.PLoS Genet 6, no. 1 (January 15, 2010): e1000810. https://doi.org/10.1371/journal.pgen.1000810.
Srivatsan A, Tehranchi A, MacAlpine DM, Wang JD. Co-orientation of replication and transcription preserves genome integrity. PLoS Genet. 2010 Jan 15;6(1):e1000810.
Srivatsan, Anjana, et al. “Co-orientation of replication and transcription preserves genome integrity.PLoS Genet, vol. 6, no. 1, Jan. 2010, p. e1000810. Pubmed, doi:10.1371/journal.pgen.1000810.
Srivatsan A, Tehranchi A, MacAlpine DM, Wang JD. Co-orientation of replication and transcription preserves genome integrity. PLoS Genet. 2010 Jan 15;6(1):e1000810.

Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

January 15, 2010

Volume

6

Issue

1

Start / End Page

e1000810

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Mutation
  • Genome, Bacterial
  • Developmental Biology
  • DNA Replication
  • Bacillus subtilis
  • 3105 Genetics
  • 0604 Genetics