Evidence map›Paper›PMID 32391871›Full record

ArticleThe Journal of cell biology2020

E3 ligase RFWD3 is a novel modulator of stalled fork stability in BRCA2-deficient cells.

Haohui Duan, Sarah Mansour, Rachel Reed, Margaret K Gillis, Benjamin Parent, Ben Liu, Zsofia Sztupinszki, Nicolai Birkbak, Zoltan Szallasi, Andrew E H Elia and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of cell biology, 2020. 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
0.9field-weighted citation impact, top 27% 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, 22 citations in OpenAlex.

  1. Article
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  6. Review
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  10. Review
  11. MicroRNA-190b Targets RFWD3 in Estrogen Receptor-Positive Breast Cancer.Breast cancer : basic and clinical research · 2024
    Article
  12. Article
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  16. Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  17. Review
  18. RPA, RFWD3 and BRCA2 at stalled forks: a balancing act.Molecular & cellular oncology · 2020
    Article
  19. 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

12 authors at 6 institutions in 2 countries.

Haohui DuanCenter for Personalized Cancer Therapy, University of Massachusetts, Boston, MA.
Sarah MansourDepartment of Biology, University of Massachusetts, Boston, MA.
Rachel ReedDana-Farber Cancer Institute, Boston, MA.
Margaret K GillisDepartment of Biology, University of Massachusetts, Boston, MA.
Benjamin ParentDana-Farber Cancer Institute, Boston, MA.
Ben LiuDana-Farber Cancer Institute, Boston, MA.
Zsofia SztupinszkiDanish Cancer Society Research Center, Copenhagen, Denmark.
Nicolai BirkbakDepartment of Molecular Medicine, Aarhus University, Aarhus, Denmark.
Zoltan SzallasiDanish Cancer Society Research Center, Copenhagen, Denmark.
Andrew E H EliaMassachusetts General Hospital, Department of Radiation Oncology, Center for Cancer Research, Boston, MA.
Judy E GarberDana-Farber Cancer Institute, Boston, MA.
Shailja PathaniaCenter for Personalized Cancer Therapy, University of Massachusetts, Boston, MA.
Dana-Farber Cancer Institute · USUniversity of Massachusetts Boston · USAarhus University · DKBoston Children's Hospital · USDanish Cancer Society · DKMassachusetts General Hospital · US

Funding

Initiative for Maximizing Student Diversity at UMass BostonR25GM076321 · NIGMS · UNIVERSITY OF MASSACHUSETTS BOSTON · PI COLON-CARMONA, ADAN, SKVIRSKY, RACHEL · 2008 to 2022
$4.5M
6 · The paper itself

Abstract

BRCA1/2 help maintain genomic integrity by stabilizing stalled forks. Here, we identify the E3 ligase RFWD3 as an essential modulator of stalled fork stability in BRCA2-deficient cells and show that codepletion of RFWD3 rescues fork degradation, collapse, and cell sensitivity upon replication stress. Stalled forks in BRCA2-deficient cells accumulate phosphorylated and ubiquitinated replication protein A (ubq-pRPA), the latter of which is mediated by RFWD3. Generation of this intermediate requires SMARCAL1, suggesting that it depends on stalled fork reversal. We show that in BRCA2-deficient cells, rescuing fork degradation might not be sufficient to ensure fork repair. Depleting MRE11 in BRCA2-deficient cells does block fork degradation, but it does not prevent fork collapse and cell sensitivity in the presence of replication stress. No such ubq-pRPA intermediate is formed in BRCA1-deficient cells, and our results suggest that BRCA1 may function upstream of BRCA2 in the stalled fork repair pathway. Collectively, our data uncover a novel mechanism by which RFWD3 destabilizes forks in BRCA2-deficient cells.

Indexed as

BRCA1 ProteinBRCA2 ProteinCell CycleCell Line, TumorCell SurvivalDNA DamageDNA HelicasesDNA RepairDNA ReplicationHumansHydroxyureaMRE11 Homologue ProteinMutationPhosphorylationRad51 RecombinaseReplication Protein ABRCA1 ProteinBRCA1 protein, humanBRCA2 ProteinBRCA2 protein, humanDNA HelicasesHydroxyureaMRE11 Homologue ProteinMRE11 protein, humanRad51 RecombinaseReplication Protein ARFWD3 protein, humanRNA, Small InterferingSMARCAL1 protein, humanUbiquitin-Protein Ligases

Identifiers

PMID32391871
PMCPMC7265328
OpenAlexW3021335614

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.