The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
BRCA2 Regulates Transcription Elongation by RNA Polymerase II to Prevent R-Loop Accumulation
Open accessAbstract
The controlled release of RNA polymerase II (RNAPII) from promoter-proximal pausing (PPP) sites is critical for transcription elongation in metazoans. We show that the human tumor suppressor BRCA2 interacts with RNAPII to regulate PPP release, thereby preventing unscheduled RNA-DNA hybrids (R-loops) implicated in genomic instability and carcinogenesis. BRCA2 inactivation by depletion or cancer-causing mutations instigates RNAPII accumulation and R-loop accrual at PPP sites in actively transcribed genes, accompanied by γH2AX formation marking DNA breakage, which is reduced by ERCC4 endonuclease depletion. BRCA2 inactivation decreases RNAPII-associated factor 1 (PAF1) recruitment (which normally promotes RNAPII release) and diminishes H2B Lys120 ubiquitination, impeding nascent RNA synthesis. PAF1 depletion phenocopies, while its overexpression ameliorates, R-loop accumulation after BRCA2 inactivation. Thus, an unrecognized role for BRCA2 in the transition from promoter-proximal pausing to productive elongation via augmented PAF1 recruitment to RNAPII is subverted by disease-causing mutations, provoking R-loop-mediated DNA breakage in BRCA2-deficient cells.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Biallelic Inactivation of BRCA2 in Fanconi Anemia
Howlett, N. G., Taniguchi, T., Olson, S., Cox, B., Waisfisz, Q., de Die-Smulders, C., Persky, N., Grompe, M., Joenje, H., Pals, G., et al. (2002) · Science · doi:10.1126/science.1073834 · Cited by 1,149
Getting up to speed with transcription elongation by RNA polymerase II
Jonkers, I., & Lis, J. T. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3953 · Cited by 876
Control of RNA Polymerase II Elongation Potential by a Novel Carboxyl-terminal Domain Kinase
Marshall, N. F., Peng, J., Xie, Z., & Price, D. H. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.43.27176 · Cited by 662 · cited 2×
“RNAPII release from PPP sites is accompanied by the phosphorylation of Ser2 in its CTD by the kinase cyclin T-CDK9 (Cho et al., 2001; Marshall et al., 1996), empowering the recruitment of a protein complex including RNAPII-associated factor 1 (PAF1) (Chen et al.”
BackgroundThe haplotype-resolved genome and epigenome of the aneuploid HeLa cancer cell line
Adey, A., Burton, J. N., Kitzman, J. O., Hiatt, J. B., Lewis, A. P., Martin, B. K., Qiu, R., Lee, C., & Shendure, J. (2013) · Nature · doi:10.1038/nature12064 · Cited by 362
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
Target gene-independent functions of MYC oncoproteins
Baluapuri, A., Wolf, E., & Eilers, M. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0215-2 · Cited by 310
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
“Interestingly, the inhibition of 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…”
BackgroundInfluentialDNA damage and transcription stress
Milano, L., Gautam, A., & Caldecott, K. W. (2024) · Molecular Cell · doi:10.1016/j.molcel.2023.11.014 · Cited by 88
Ligands stimulating antitumour immunity as the next G-quadruplex challenge
Miglietta, G., Marinello, J., Russo, M., & Capranico, G. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01649-y · Cited by 44
“Moreover, BRCA2 gene inactivation can cause site-specific formation of unscheduled R-loops and a ERCC4 endonuclease-mediated DNA breaks [129].”
Background
Metadata
- Authors
- Shivji, M. K. K., Renaudin, X., Williams, Ç. H., & Venkitaraman, A. R.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 22
- Issue
- 4
- Pages
- 1031-1039
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2784889917
- Cited by
- 159
- References
- 4
- FWCI
- 5.34
- Type
- journal article
- Language
- en
- Open access
- gold
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: BRCA2 Regulates Transcription Elongation by RNA Polymerase II to Prevent R-Loop Accumulation. https://app.cochat.ai/papers/10.1016/j.celrep.2017.12.086
- The paper
- Shivji, M. K. K., Renaudin, X., Williams, Ç. H., & Venkitaraman, A. R. (2018). BRCA2 Regulates Transcription Elongation by RNA Polymerase II to Prevent R-Loop Accumulation. Cell Reports. https://doi.org/10.1016/j.celrep.2017.12.086
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
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.
