Evidence map›Paper›PMID 34599155›Full record

ArticleCell death & disease2021

BRCA1 prevents R-loop-associated centromeric instability.

Carine Racca, Sébastien Britton, Sabrine Hédouin, Claire Francastel, Patrick Calsou, Florence Larminat

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
7.3field-weighted citation impact, top 3% 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

33 citing papers in PubMed, 49 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Article
  6. Preserving centromere identity: right amounts of CENP-A at the right place and time.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2025
    Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Repetitive Sequence Stability in Embryonic Stem Cells.International journal of molecular sciences · 2024
    Review
  17. Article
  18. Heliyon · 2024
    Article
  19. DNA strand breaks at centromeres: Friend or foe?Seminars in cell & developmental biology · 2024
    Review
  20. Article
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

6 authors at 1 institution in 2 countries.

Carine RaccaInstitut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France.
Sébastien BrittonInstitut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France.
Sabrine HédouinUniversité de Paris, Epigénétique et Destin Cellulaire, CNRS, Paris, F-75013, France.
Claire FrancastelUniversité de Paris, Epigénétique et Destin Cellulaire, CNRS, Paris, F-75013, France.
Patrick CalsouInstitut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France.ORCID 0000-0001-7951-9806
Florence LarminatInstitut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France. larminat@ipbs.fr.ORCID 0000-0002-3389-2717
Centre National de la Recherche Scientifique · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Centromeres are defined by chromatin containing the histone H3 variant CENP-A assembled onto repetitive α-satellite sequences, which are actively transcribed throughout the cell cycle. Centromeres play an essential role in chromosome inheritance and genome stability through coordinating kinetochores assembly during mitosis. Structural and functional alterations of the centromeres cause aneuploidy and chromosome aberrations which can induce cell death. In human cells, the tumor suppressor BRCA1 associates with centromeric chromatin in the absence of exogenous damage. While we previously reported that BRCA1 contributes to proper centromere homeostasis, the mechanism underlying its centromeric function and recruitment was not fully understood. Here, we show that BRCA1 association with centromeric chromatin depends on the presence of R-loops, which are non-canonical three-stranded structures harboring a DNA:RNA hybrid and are frequently formed during transcription. Subsequently, BRCA1 counteracts the accumulation of R-loops at centromeric α-satellite repeats. Strikingly, BRCA1-deficient cells show impaired localization of CENP-A, higher transcription of centromeric RNA, increased breakage at centromeres and formation of acentric micronuclei, all these features being R-loop-dependent. Finally, BRCA1 depletion reveals a Rad52-dependent hyper-recombination process between centromeric satellite repeats, associated with centromere instability and missegregation. Altogether, our findings provide molecular insights into the key function of BRCA1 in maintaining centromere stability and identity.

Indexed as

R-Loop StructuresBRCA1 ProteinCell Line, TumorCentromereDNA Breaks, Double-StrandedDNA, SatelliteHumansModels, BiologicalRad52 DNA Repair and Recombination ProteinRecombination, GeneticBRCA1 ProteinDNA, SatelliteRad52 DNA Repair and Recombination ProteinRAD52 protein, human

Identifiers

PMID34599155
PMCPMC8486751
OpenAlexW3202933076

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.