Evidence map›Paper›PMID 33707212›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

Super-resolution mapping of cellular double-strand break resection complexes during homologous recombination.

Donna R Whelan, Eli Rothenberg

Open access · hybridAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.8field-weighted citation impact, top 8% 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

25 citing papers in PubMed, 49 citations in OpenAlex.

  1. Review
  2. Plant tolerance mechanisms to DNA-damaging UV stress.Journal of experimental botany · 2025
    Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Key molecular DNA damage responses of human cells to radiation.Frontiers in cell and developmental biology · 2024
    Review
  12. Article
  13. Dynamic Properties of the DNA Damage Response Mre11/Rad50 Complex.International journal of molecular sciences · 2023
    Review
  14. Article
  15. Genome Protection by DNA Polymerase θ.Annual review of genetics · 2022
    Review
  16. Article
  17. DNA Holliday Junction: History, Regulation and Bioactivity.International journal of molecular sciences · 2022
    Review
  18. Article
  19. 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

2 authors at 2 institutions in 2 countries.

Donna R WhelanDepartment of Pharmacy and Biomedical Sciences, La Trobe Institute for Molecular Science, La Trobe University, Bendigo, VIC 3552, Australia; d.whelan@latrobe.edu.au eli.rothenberg@nyulangone.org.ORCID 0000-0002-7078-5443
Eli RothenbergDepartment of Biochemistry and Molecular Pharmacology, Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016 d.whelan@latrobe.edu.au eli.rothenberg@nyulangone.org.ORCID 0000-0002-1382-1380
La Trobe University · AUNew York University · US

Funding

Structural determinants of Pol theta functionP01CA247773 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DALE A RAMSDEN · 2020 to 2026
$15.2M
Mechanisms of Human DNA Double-Strand Break Repair via Quantitative Single-Molecule Imaging - Equipment SupplementR35GM134947 · NIGMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Eli Rothenberg · 2020 to 2026
$3.4M
Mechanism and Fidelity of RAG mediated DNA recombinationR01AI153040 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ROTHENBERG, ELI · 2020 to 2024
$2.7M
NIGMS NIH HHS R35 GM134947
6 · The paper itself

Abstract

Homologous recombination (HR) is a major pathway for repair of DNA double-strand breaks (DSBs). The initial step that drives the HR process is resection of DNA at the DSB, during which a multitude of nucleases, mediators, and signaling proteins accumulates at the damage foci in a manner that remains elusive. Using single-molecule localization super-resolution (SR) imaging assays, we specifically visualize the spatiotemporal behavior of key mediator and nuclease proteins as they resect DNA at single-ended double-strand breaks (seDSBs) formed at collapsed replication forks. By characterizing these associations, we reveal the in vivo dynamics of resection complexes involved in generating the long single-stranded DNA (ssDNA) overhang prior to homology search. We show that 53BP1, a protein known to antagonize HR, is recruited to seDSB foci during early resection but is spatially separated from repair activities. Contemporaneously, CtBP-interacting protein (CtIP) and MRN (MRE11-RAD51-NBS1) associate with seDSBs, interacting with each other and BRCA1. The HR nucleases EXO1 and DNA2 are also recruited and colocalize with each other and with the repair helicase Bloom syndrome protein (BLM), demonstrating multiple simultaneous resection events. Quantification of replication protein A (RPA) accumulation and ssDNA generation shows that resection is completed 2 to 4 h after break induction. However, both BRCA1 and BLM persist later into HR, demonstrating potential roles in homology search and repair resolution. Furthermore, we show that initial recruitment of BRCA1 and removal of Ku are largely independent of MRE11 exonuclease activity but dependent on MRE11 endonuclease activity. Combined, our observations provide a detailed description of resection during HR repair.

Indexed as

DNA Breaks, Double-StrandedHomologous RecombinationRecombinational DNA RepairSingle Molecule ImagingBRCA1 ProteinCell Line, TumorDNA HelicasesDNA Repair EnzymesDNA, Single-StrandedEndodeoxyribonucleasesExodeoxyribonucleasesHumansMRE11 Homologue ProteinMultiprotein ComplexesRecQ HelicasesTumor Suppressor p53-Binding Protein 1Bloom syndrome proteinBRCA1 ProteinBRCA1 protein, humanDNA2 protein, humanDNA HelicasesDNA Repair EnzymesDNA, Single-StrandedEndodeoxyribonucleasesEXO1 protein, humanExodeoxyribonucleasesMRE11 Homologue ProteinMRE11 protein, humanMultiprotein ComplexesRBBP8 protein, humanRecQ HelicasesTP53BP1 protein, humanTumor Suppressor p53-Binding Protein 1BRCA1DNA damageDNA repairhomologous recombinationresection

Identifiers

PMID33707212
PMCPMC7980414
OpenAlexW3135485886

What OpenQuestion holds

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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.