The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
R-loop-mediated genomic instability is caused by impairment of replication fork progression
Open accessAbstract
Transcriptional R loops are anomalous RNA:DNA hybrids that have been detected in organisms from bacteria to humans. These structures have been shown in eukaryotes to result in DNA damage and rearrangements; however, the mechanisms underlying these effects have remained largely unknown. To investigate this, we first show that R-loop formation induces chromosomal DNA rearrangements and recombination in Escherichia coli , just as it does in eukaryotes. More importantly, we then show that R-loop formation causes DNA replication fork stalling, and that this in fact underlies the effects of R loops on genomic stability. Strikingly, we found that attenuation of replication strongly suppresses R-loop-mediated DNA rearrangements in both E. coli and HeLa cells. Our findings thus provide a direct demonstration that R-loop formation impairs DNA replication and that this is responsible for the deleterious effects of R loops on genome stability from bacteria to humans.
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Cites
DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139
Rogakou, E. P., Pilch, D. R., Orr, A. H., Ivanova, V. S., & Bonner, W. M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.10.5858 · Cited by 5,438
Thermodynamic parameters to predict stability of RNA/DNA hybrid duplexes
Sugimoto, N., Nakano, S.-I., Katoh, M., Matsumura, A., Nakamuta, H., Ohmichi, T., Yoneyama, M., & Sasaki, M. (1995) · Biochemistry · doi:10.1021/bi00035a029 · Cited by 697 · cited 1×
“For example, it has been known for some time that G-rich regions in nascent transcripts favor R-loop formation due to the exceptional stability of rG:dC base pairs (Sugimoto et al. 1995).”
BackgroundReplication 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
After 30 Years of Study, the Bacterial SOS Response Still Surprises Us
Michel, B. (2005) · PLoS Biology · doi:10.1371/journal.pbio.0030255 · Cited by 327
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
The MMS22L-TONSL Complex Mediates Recovery from Replication Stress and Homologous Recombination
O'Donnell, L., Panier, S., Wildenhain, J., Tkach, J. M., Al-Hakim, A., Landry, M.-C., Escribano-Diaz, C., Szilard, R. K., Young, J. T. F., Munro, M., et al. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.10.024 · Cited by 149
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
BRCA2 prevents R-loop accumulation and associates with TREX-2 mRNA export factor PCID2
Bhatia, V., Barroso, S. I., García-Rubio, M. L., Tumini, E., Herrera-Moyano, E., & Aguilera, A. (2014) · Nature · doi:10.1038/nature13374 · Cited by 537
Skourti-Stathaki, K., & Proudfoot, N. J. (2014) · Genes & Development · doi:10.1101/gad.242990.114 · Cited by 532
The Fanconi Anemia Pathway Maintains Genome Stability by Coordinating Replication and Transcription
Schwab, R. A., Nieminuszczy, J., Shah, F., Langton, J., Lopez Martinez, D., Liang, C.-C., Cohn, M. A., Gibbons, R. J., Deans, A. J., & Niedzwiedz, W. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.09.012 · Cited by 361
Increased global transcription activity as a mechanism of replication stress in cancer
Kotsantis, P., Silva, L. M., Irmscher, S., Jones, R. M., Folkes, L., Gromak, N., & Petermann, E. (2016) · Nature Communications · doi:10.1038/ncomms13087 · Cited by 336
Metadata
- Authors
- Gan, W., Guan, Z., Liu, J., Gui, T., Shen, K., Manley, J. L., & Li, X.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2011-10-01
- Volume
- 25
- Issue
- 19
- Pages
- 2041-2056
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2104301158
- Cited by
- 457
- References
- 6
- Type
- posted content
- Language
- en
- Open access
- diamond
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- Gan, W., Guan, Z., Liu, J., Gui, T., Shen, K., Manley, J. L., & Li, X. (2011). R-loop-mediated genomic instability is caused by impairment of replication fork progression. Genes & Development. https://doi.org/10.1101/gad.17010011
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