The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Linking RNA Polymerase Backtracking to Genome Instability in E. coli
Open accessAbstract
SUMMARY Frequent co-directional collisions between the replisome and RNA polymerase (RNAP) are inevitable because the rate of replication is much faster than that of transcription. Here we show that the outcome of such collisions depends on the productive state of transcription elongation complexes (ECs). Co-directional collisions with backtracked (arrested) ECs lead to DNA double strand breaks (DSBs), whereas head-on collisions do not. A mechanistic model is proposed to explain backtracking-mediated DSBs. We further show that bacteria employ various strategies to evade replisome collisions with backtracked RNAP, the most general of which is translation that prevents RNAP backtracking. If translation is abrogated, DSBs are suppressed by elongation factors that either prevent backtracking or reactivate backtracked ECs. Finally, termination factors also contribute to genomic stability by removing arrested ECs. Our results establish RNAP backtracking as the intrinsic hazard to chromosomal integrity and implicate active ribosomes and other anti-backtracking mechanisms in genome maintenance.
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Cites
The complete genome sequence of the gram-positive bacterium Bacillus subtilis.
Kunst, F., Ogasawara, N., Moszer, I., Albertini, A. M., Alloni, G., Azevedo, V., Bertero, M. G., Bessières, P., Bolotin, A., Borchert, S., et al. (1997) · Nature · doi:10.1038/36786 · Cited by 3,679
Mutation as a Stress Response and the Regulation of Evolvability
Galhardo, R. S., Hastings, P. J., & Rosenberg, S. M. (2007) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409230701648502 · Cited by 643
Replication fork stalling at natural impediments
Mirkin, E. V., & Mirkin, S. M. (2007) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00030-06 · Cited by 482
Structural basis of RNA polymerase II backtracking, arrest and reactivation
Cheung, A. C. M., & Cramer, P. (2011) · Nature · doi:10.1038/nature09785 · Cited by 373
Control of rRNA transcription in Escherichia coli
Condon, C., Squires, C., & Squires, C. L. (1995) · Microbiological Reviews · doi:10.1128/mr.59.4.623-645.1995 · Cited by 349
Direct restart of a replication fork stalled by a head-on RNA polymerase
Pomerantz, R. T., & O’Donnell, M. (2010) · Science · doi:10.1126/science.1179595 · Cited by 150
Cited by
R-Loops as Cellular Regulators and Genomic Threats
Crossley, M. P., Bocek, M., & Cimprich, K. A. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.01.024 · Cited by 746
Aguilera, A., & García-Muse, T. (2013) · Annual Review of Genetics · doi:10.1146/annurev-genet-111212-133232 · Cited by 476
Mechanisms of Oncogene-Induced Replication Stress: Jigsaw Falling into Place
Kotsantis, P., Petermann, E., & Boulton, S. J. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-1461 · Cited by 416
Transcription-replication encounters, consequences and genomic instability
Helmrich, A., Ballarino, M., Nudler, E., & Tora, L. (2013) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2543 · Cited by 265
Self-citationSaponaro, M., Kantidakis, T., Mitter, R., Kelly, G. P., Heron, M., Williams, H., Söding, J., Stewart, A., & Svejstrup, J. Q. (2014) · Cell · doi:10.1016/j.cell.2014.03.048 · Cited by 207
Metadata
- Authors
- Dutta, D., Shatalin, K., Epshtein, V., Gottesman, M. E., & Nudler, E.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2011-08
- Volume
- 146
- Issue
- 4
- Pages
- 533-543
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1999718691
- Cited by
- 320
- References
- 6
- FWCI
- 11.51
- Type
- journal article
- Language
- en
- Open access
- bronze
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