Evidence map›Paper›PMID 29386125›Full record

ArticleCell reports2018

BRCA2 Regulates Transcription Elongation by RNA Polymerase II to Prevent R-Loop Accumulation.

Mahmud K K Shivji, Xavier Renaudin, Çiğdem H Williams, Ashok R Venkitaraman

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed
6.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

109 citing papers in PubMed, 154 citations in OpenAlex.

  1. Review
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  13. The function of Mgs1/WRNIP1 in genome maintenance.Frontiers in molecular biosciences · 2026
    Review
  14. Review
  15. Article
  16. G-quadruplexes as a source of vulnerability in BRCA2Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  17. Review
  18. Review
  19. Article
  20. R-loops: a key driver of inflammatory responses in cancer.Experimental & molecular medicine · 2025
    Review

49 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Mahmud K K ShivjiMedical Research Council Cancer Unit, University of Cambridge, Hills Road, Cambridge CB2 0XZ, UK.
Xavier RenaudinMedical Research Council Cancer Unit, University of Cambridge, Hills Road, Cambridge CB2 0XZ, UK.
Çiğdem H WilliamsMedical Research Council Cancer Unit, University of Cambridge, Hills Road, Cambridge CB2 0XZ, UK.
Ashok R VenkitaramanMedical Research Council Cancer Unit, University of Cambridge, Hills Road, Cambridge CB2 0XZ, UK. Electronic address: arv22@mrc-cu.cam.ac.uk.
Medical Research Council · GBUniversity of Cambridge · GB

Funding

Medical Research Council G1001521Medical Research Council MC_UU_12022/1Medical Research Council MC_UU_12022/8Medical Research Council MR/N501876/1
6 · The paper itself

Abstract

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.

Indexed as

BRCA2 ProteinHumansRNA Polymerase IITranscriptional ActivationTranscription FactorsTranscription, GeneticBRCA2 ProteinBRCA2 protein, humanRNA Polymerase IITranscription FactorsBRCA2genomic instabilityPAF1R-loopsRNA polymerase IItranscription elongation

Identifiers

PMID29386125
PMCPMC5846855
OpenAlexW2784889917

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.