The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Co-transcriptional R-loops are the main cause of estrogen-induced DNA damage
Open accessAbstract
The hormone estrogen (E2) binds the estrogen receptor to promote transcription of E2-responsive genes in the breast and other tissues. E2 also has links to genomic instability, and elevated E2 levels are tied to breast cancer. Here, we show that E2 stimulation causes a rapid, global increase in the formation of R-loops, co-transcriptional RNA-DNA products, which in some instances have been linked to DNA damage. We show that E2-dependent R-loop formation and breast cancer rearrangements are highly enriched at E2-responsive genomic loci and that E2 induces DNA replication-dependent double-strand breaks (DSBs). Strikingly, many DSBs that accumulate in response to E2 are R-loop dependent. Thus, R-loops resulting from the E2 transcriptional response are a significant source of DNA damage. This work reveals a novel mechanism by which E2 stimulation leads to genomic instability and highlights how transcriptional programs play an important role in shaping the genomic landscape of DNA damage susceptibility.
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Cites
GREAT improves functional interpretation of cis-regulatory regions
McLean, C. Y., Bristor, D., Hiller, M., Clarke, S. L., Schaar, B. T., Lowe, C. B., Wenger, A. M., & Bejerano, G. (2010) · Nature Biotechnology · doi:10.1038/nbt.1630 · Cited by 4,502
Landscape of somatic mutations in 560 breast cancer whole-genome sequences
Nik-Zainal, S., Davies, H., Staaf, J., Ramakrishna, M., Glodzik, D., Zou, X., Martincorena, I., Alexandrov, L. B., Martin, S., Wedge, D. C., et al. (2016) · Nature · doi:10.1038/nature17676 · Cited by 2,218
Cited by
Endogenous DNA damage as a source of genomic instability in cancer
Tubbs, A., & Nussenzweig, A. (2017) · Cell · doi:10.1016/j.cell.2017.01.002 · Cited by 1,452
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
Self-citationCristini, A., Groh, M., Kristiansen, M. S., & Gromak, N. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.04.025 · Cited by 423
De Magis, A., Manzo, S. G., Russo, M., Marinello, J., Morigi, R., Sordet, O., & Capranico, G. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1810409116 · Cited by 332
Chen, L., Chen, J.-Y., Huang, Y.-J., Gu, Y., Qiu, J., Qian, H., Shao, C., Zhang, X., Hu, J., Li, H., et al. (2018) · Molecular Cell · doi:10.1016/j.molcel.2017.12.029 · Cited by 299
Metadata
- Authors
- Stork, C. T., Bocek, M., Crossley, M. P., Sollier, J., Sanz, L. A., Chédin, F., Swigut, T., & Cimprich, K. A.
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2016-08-23
- Volume
- 5
- ISSN
- 2050-084X (ISSN-L)
- OpenAlex
- W2515159273
- Cited by
- 303
- References
- 2
- FWCI
- 11.44
- Type
- journal article
- Language
- en
- Open access
- gold
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- Stork, C. T., Bocek, M., Crossley, M. P., Sollier, J., Sanz, L. A., Chédin, F., Swigut, T., & Cimprich, K. A. (2016). Co-transcriptional R-loops are the main cause of estrogen-induced DNA damage. eLife. https://doi.org/10.7554/elife.17548
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