Evidence map›Paper›PMID 37823591›Full record

ArticleNucleic acids research2023

BRCA1-BARD1 combines multiple chromatin recognition modules to bridge nascent nucleosomes.

Hayden Burdett, Martina Foglizzo, Laura J Musgrove, Dhananjay Kumar, Gillian Clifford, Lisa J Campbell, George R Heath, Elton Zeqiraj, Marcus D Wilson

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

17 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Article
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  4. Article
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  7. Article
  8. Article
  9. Review
  10. Article
  11. Role of BRCA1 in glioblastoma etiology.Cellular oncology (Dordrecht, Netherlands) · 2024
    Review
  12. Article
  13. Article
  14. DOT1L-mediated RAP80 methylation promotes BRCA1 recruitment to elicit DNA repair.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  15. Article
  16. Article
  17. Review
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

9 authors at 2 institutions in 1 country.

Hayden BurdettWellcome Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Kings Buildings, Mayfield Road, Edinburgh EH9 3JR, UK.
Martina FoglizzoAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.ORCID 0000-0001-9132-4737
Laura J MusgroveAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
Dhananjay KumarWellcome Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Kings Buildings, Mayfield Road, Edinburgh EH9 3JR, UK.
Gillian CliffordWellcome Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Kings Buildings, Mayfield Road, Edinburgh EH9 3JR, UK.
Lisa J CampbellAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
George R HeathAstbury Centre for Structural Molecular Biology, School of Physics & Astronomy and Biomedical Sciences, Faculty of Engineering & Physical Sciences and Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
Elton ZeqirajAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
Marcus D WilsonWellcome Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Kings Buildings, Mayfield Road, Edinburgh EH9 3JR, UK.ORCID 0000-0001-9551-5514
University of Leeds · GBWellcome Centre for Cell Biology · GB

Funding

Medical Research Council MR/T029471/1Wellcome Trust 200523/Z/16/Z
6 · The paper itself

Abstract

Chromatin association of the BRCA1-BARD1 heterodimer is critical to promote homologous recombination repair of DNA double-strand breaks (DSBs) in S/G2. How the BRCA1-BARD1 complex interacts with chromatin that contains both damage induced histone H2A ubiquitin and inhibitory H4K20 methylation is not fully understood. We characterised BRCA1-BARD1 binding and enzymatic activity to an array of mono- and di-nucleosome substrates using biochemical, structural and single molecule imaging approaches. We found that the BRCA1-BARD1 complex preferentially interacts and modifies di-nucleosomes over mono-nucleosomes, allowing integration of H2A Lys-15 ubiquitylation signals with other chromatin modifications and features. Using high speed- atomic force microscopy (HS-AFM) to monitor how the BRCA1-BARD1 complex recognises chromatin in real time, we saw a highly dynamic complex that bridges two nucleosomes and associates with the DNA linker region. Bridging is aided by multivalent cross-nucleosome interactions that enhance BRCA1-BARD1 E3 ubiquitin ligase catalytic activity. Multivalent interactions across nucleosomes explain how BRCA1-BARD1 can recognise chromatin that retains partial di-methylation at H4 Lys-20 (H4K20me2), a parental histone mark that blocks BRCA1-BARD1 interaction with nucleosomes, to promote its enzymatic and DNA repair activities.

Indexed as

BRCA1 ProteinChromatinNucleosomesUbiquitin-Protein LigasesHeLa CellsHistonesHumansTumor Suppressor ProteinsBARD1 protein, humanBRCA1 ProteinBRCA1 protein, humanChromatinHistonesNucleosomesTumor Suppressor ProteinsUbiquitin-Protein Ligases

Identifiers

PMID37823591
PMCPMC10639053
OpenAlexW4387564037

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.