Evidence map›Paper›PMID 34726323›Full record

ArticleEMBO reports2021

Two redundant ubiquitin-dependent pathways of BRCA1 localization to DNA damage sites.

Alana Sherker, Natasha Chaudhary, Salomé Adam, Anne Margriet Heijink, Sylvie M Noordermeer, Amélie Fradet-Turcotte, Daniel Durocher

Open access · bronzeAbstract read
In one paragraph

Article in EMBO reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

19 citing papers in PubMed, 21 citations in OpenAlex.

  1. Mechanisms and disease relevance of DNA break repair pathway choice.Nature reviews. Molecular cell biology · 2026
    Review
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  7. Systematic analysis ofTranslational andrology and urology · 2026
    Article
  8. Review
  9. Article
  10. 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
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. BRCA1/BARD1 is a nucleosome reader and writer.Trends in biochemical sciences · 2022
    Review
  18. Article
  19. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Alana SherkerLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.ORCID 0000-0001-5827-4678
Natasha ChaudharyLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
Salomé AdamLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
Anne Margriet HeijinkLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.ORCID 0000-0001-9229-0575
Sylvie M NoordermeerLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.ORCID 0000-0003-2737-9690
Amélie Fradet-TurcotteCHU de Québec Research Center-Université Laval (L'Hôtel-Dieu de Québec), Cancer Research Center, Québec, QC, Canada.ORCID 0000-0002-5431-8650
Daniel DurocherLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.ORCID 0000-0003-3863-8635
Mount Sinai Hospital · CAHôtel-Dieu de Québec · CA

Funding

CIHR FDN143343
6 · The paper itself

Abstract

The tumor suppressor BRCA1 accumulates at sites of DNA damage in a ubiquitin-dependent manner. In this work, we revisit the role of RAP80 in promoting BRCA1 recruitment to damaged chromatin. We find that RAP80 acts redundantly with the BRCA1 RING domain to promote BRCA1 recruitment to DNA damage sites. We show that that RNF8 E3 ligase acts upstream of both the RAP80- and RING-dependent activities, whereas RNF168 acts uniquely upstream of the RING domain. BRCA1 RING mutations that do not impact BARD1 interaction, such as the E2 binding-deficient I26A mutation, render BRCA1 unable to accumulate at DNA damage sites in the absence of RAP80. Cells that combine BRCA1 I26A and mutations that disable the RAP80-BRCA1 interaction are hypersensitive to PARP inhibition and are unable to form RAD51 foci. Our results suggest that in the absence of RAP80, the BRCA1 E3 ligase activity is necessary for recognition of histone H2A Lys13/Lys15 ubiquitylation by BARD1, although we cannot rule out the possibility that the BRCA1 RING facilitates ubiquitylated nucleosome recognition in other ways.

Indexed as

Nuclear ProteinsUbiquitinBRCA1 ProteinCarrier ProteinsDNA-Binding ProteinsDNA DamageDNA RepairHistone ChaperonesUbiquitin-Protein LigasesBRCA1 ProteinCarrier ProteinsDNA-Binding ProteinsHistone ChaperonesNuclear ProteinsUbiquitinUbiquitin-Protein LigasesBARD1BRCA1DNA damageRAP80ubiquitin

Identifiers

PMID34726323
PMCPMC8647010
OpenAlexW3211209509

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.