The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Attenuation of RNA polymerase II pausing mitigates BRCA1-associated R-loop accumulation and tumorigenesis
Open accessAbstract
Most BRCA1-associated breast tumours are basal-like yet originate from luminal progenitors. BRCA1 is best known for its functions in double-strand break repair and resolution of DNA replication stress. However, it is unclear whether loss of these ubiquitously important functions fully explains the cell lineage-specific tumorigenesis. In vitro studies implicate BRCA1 in elimination of R-loops, DNA-RNA hybrid structures involved in transcription and genetic instability. Here we show that R-loops accumulate preferentially in breast luminal epithelial cells, not in basal epithelial or stromal cells, of BRCA1 mutation carriers. Furthermore, R-loops are enriched at the 5′ end of those genes with promoter-proximal RNA polymerase II (Pol II) pausing. Genetic ablation of Cobra1, which encodes a Pol II-pausing and BRCA1-binding protein, ameliorates R-loop accumulation and reduces tumorigenesis in Brca1-knockout mouse mammary epithelium. Our studies show that Pol II pausing is an important contributor to BRCA1-associated R-loop accumulation and breast cancer development.
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kConFab, Lim, E., Vaillant, F., Wu, D., Forrest, N. C., Pal, B., Hart, A. H., Asselin-Labat, M.-L., Gyorki, D. E., Ward, T., et al. (2009) · Nature Medicine · doi:10.1038/nm.2000 · Cited by 1,492 · cited 1×
“05; (2) TSS with common R-loop peaks only present in B1.”
Schlacher, K., Wu, H., & Jasin, M. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.05.015 · Cited by 936
Mechanisms of BRCA1 Tumor Suppression
Silver, D. P., & Livingston, D. M. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0221 · Cited by 159
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
Born to run: control of transcription elongation by RNA polymerase II
Chen, F. X., Smith, E. R., & Shilatifard, A. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0010-5 · Cited by 447
Bossaert, M., Pipier, A., Riou, J.-F., Noirot, C., Nguyên, L.-T., Serre, R.-F., Bouchez, O., Defrancq, E., Calsou, P., Britton, S., et al. (2021) · eLife · doi:10.7554/elife.65184 · Cited by 97
“…BRD4 and TOP1 activities as well as the reduction of RNA-Pol elongation has been shown to promote R-loops (Shivji et al., 2018; Tuduri et al., 2009; Zhang et al., 2017; Kim et al., 2019; El Hage et al., 2010; Li et al., 2015), a DNA-RNA secondary structure associated with the formation of…”
BackgroundAAV-mediated genome editing is influenced by the formation of R-loops
Puzzo, F., Crossley, M. P., Goswami, A., Zhang, F., Pekrun, K., Garzon, J. L., Cimprich, K. A., & Kay, M. A. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.09.035 · Cited by 4
Metadata
- Authors
- Zhang, X., Chiang, H.-C., Wang, Y., Zhang, C., Smith, S., Zhao, X., Nair, S. J., Michalek, J., Jatoi, I., Lautner, M., Oliver, B., Wang, H., Petit, A., Soler, T., Brunet, J., Mateo, F., Angel Pujana, M., Poggi, E., Chaldekas, K., Isaacs, C., Peshkin, B. N., Ochoa, O., Chedin, F., Theoharis, C., Sun, L.-Z., Curiel, T. J., Elledge, R., Jin, V. X., Hu, Y., & Li, R.
- Venue
- Nature Communications
- Published
- 2017-06-26
- Volume
- 8
- Issue
- 1
- Pages
- 15908-15908
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2715937868
- Cited by
- 158
- References
- 3
- FWCI
- 8.67
- Type
- journal article
- Language
- en
- Open access
- gold
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- Zhang, X., Chiang, H.-C., Wang, Y., Zhang, C., Smith, S., Zhao, X., Nair, S. J., Michalek, J., Jatoi, I., Lautner, M., Oliver, B., Wang, H., Petit, A., Soler, T., Brunet, J., Mateo, F., Angel Pujana, M., Poggi, E., Chaldekas, K., . . . Li, R. (2017). Attenuation of RNA polymerase II pausing mitigates BRCA1-associated R-loop accumulation and tumorigenesis. Nature Communications. https://doi.org/10.1038/ncomms15908
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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.
