The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
EWS–FLI1 increases transcription to cause R-loops and block BRCA1 repair in Ewing sarcoma
Open accessAbstract
Ewing sarcoma is an aggressive paediatric cancer of the bone and soft tissue. It results from a chromosomal translocation, predominantly t(11;22)(q24:q12), that fuses the N-terminal transactivation domain of the constitutively expressed EWSR1 protein with the C-terminal DNA binding domain of the rarely expressed FLI1 protein. Ewing sarcoma is highly sensitive to genotoxic agents such as etoposide, but the underlying molecular basis of this sensitivity is unclear. Here we show that Ewing sarcoma cells display alterations in regulation of damage-induced transcription, accumulation of R-loops and increased replication stress. In addition, homologous recombination is impaired in Ewing sarcoma owing to an enriched interaction between BRCA1 and the elongating transcription machinery. Finally, we uncover a role for EWSR1 in the transcriptional response to damage, suppressing R-loops and promoting homologous recombination. Our findings improve the current understanding of EWSR1 function, elucidate the mechanistic basis of the sensitivity of Ewing sarcoma to chemotherapy (including PARP1 inhibitors) and highlight a class of BRCA-deficient-like tumours.
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Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890
Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
Farmer, H., McCabe, N., Lord, C. J., Tutt, A. N. J., Johnson, D. A., Richardson, T. B., Santarosa, M., Dillon, K. J., Hickson, I., Knights, C., et al. (2005) · Nature · doi:10.1038/nature03445 · Cited by 6,683
Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase
Bryant, H. E., Schultz, N., Thomas, H. D., Parker, K. M., Flower, D., Lopez, E., Kyle, S., Meuth, M., Curtin, N. J., & Helleday, T. (2005) · Nature · doi:10.1038/nature03443 · Cited by 5,198
Cited by
Grünewald, T. G. P., Cidre-Aranaz, F., Surdez, D., Tomazou, E. M., de Álava, E., Kovar, H., Sorensen, P. H., Delattre, O., & Dirksen, U. (2018) · Nature Reviews Disease Primers · doi:10.1038/s41572-018-0003-x · Cited by 873
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
R Loops: From Physiological to Pathological Roles
García-Muse, T., & Aguilera, A. (2019) · Cell · doi:10.1016/j.cell.2019.08.055 · Cited by 697
Zhang, C., Chen, L., Peng, D., Jiang, A., He, Y., Zeng, Y., Xie, C., Zhou, H., Luo, X., Liu, H., et al. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.06.017 · Cited by 331
crisprSQL: a novel database platform for CRISPR/Cas off-target cleavage assays
Störtz, F., & Minary, P. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkaa885 · Cited by 37
Metadata
- Authors
- Gorthi, A., Romero, J. C., Loranc, E., Cao, L., Lawrence, L. A., Goodale, E., Iniguez, A. B., Bernard, X., Masamsetti, V. P., Roston, S., Lawlor, E. R., Toretsky, J. A., Stegmaier, K., Lessnick, S. L., Chen, Y., & Bishop, A. J. R.
- Venue
- Nature
- Published
- 2018-03-07
- Volume
- 555
- Issue
- 7696
- Pages
- 387-391
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2792813139
- Cited by
- 329
- References
- 4
- FWCI
- 19.61
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: EWS–FLI1 increases transcription to cause R-loops and block BRCA1 repair in Ewing sarcoma. https://app.cochat.ai/papers/10.1038/nature25748
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- Gorthi, A., Romero, J. C., Loranc, E., Cao, L., Lawrence, L. A., Goodale, E., Iniguez, A. B., Bernard, X., Masamsetti, V. P., Roston, S., Lawlor, E. R., Toretsky, J. A., Stegmaier, K., Lessnick, S. L., Chen, Y., & Bishop, A. J. R. (2018). EWS–FLI1 increases transcription to cause R-loops and block BRCA1 repair in Ewing sarcoma. Nature. https://doi.org/10.1038/nature25748
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
