Evidence map›Paper›PMID 37717054›Full record

ArticleNature communications2023

Genome-wide analysis of DNA-PK-bound MRN cleavage products supports a sequential model of DSB repair pathway choice.

Rajashree A Deshpande, Alberto Marin-Gonzalez, Hannah K Barnes, Phillip R Woolley, Taekjip Ha, Tanya T Paull

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

16 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
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  8. Differential expression of a disease-associatedbioRxiv : the preprint server for biology · 2025
    Article
  9. Article
  10. Review
  11. ER-associated degradation ligase HRD1 links ER stress to DNA damage repair by modulating the activity of DNA-PKcs.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Fluorogenic CRISPR for genomic DNA imaging.Nature communications · 2024
    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 3 institutions in 1 country.

Rajashree A DeshpandeEncoded Therapeutics, 341 Oyster Point Blvd, South San Francisco, CA, 94080, USA.
Alberto Marin-GonzalezDepartment of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Hannah K BarnesThe Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, 78712, USA.ORCID http://orcid.org/0009-0001-3398-534X
Phillip R WoolleyThe Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, 78712, USA.
Taekjip HaDepartment of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-2195-6258
Tanya T PaullThe Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, 78712, USA. tpaull@utexas.edu.ORCID http://orcid.org/0000-0002-2991-651X
The University of Texas at Austin · USHoward Hughes Medical Institute · USRapt Therapeutics (United States) · US

Funding

Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI John A. Tainer · 2001 to 2026
$89.6M
Single Molecule Studies of Nucleic Acids RemodelingR35GM122569 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI Taekjip Ha · 2017 to 2026
$3.5M
Chromatin Function During Transcription and DNA Repair at Single Molecule Resolutionin Living CellsU01DK127432 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI HA, TAEKJIP, JOHNSON, MARGARET ELLEN · 2020 to 2024
$3.5M
DNA end processing by the Mre11/Rad50/Nbs1 complex in human cellsR01GM138548 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI PAULL, TANYA T · 2021 to 2024
$1.2M
NCI NIH HHS P01 CA092584NIDDK NIH HHS U01 DK127432NIGMS NIH HHS R01 GM138548NIGMS NIH HHS R35 GM122569
6 · The paper itself

Abstract

The Mre11-Rad50-Nbs1 (MRN) complex recognizes and processes DNA double-strand breaks for homologous recombination by performing short-range removal of 5' strands. Endonucleolytic processing by MRN requires a stably bound protein at the break site-a role we postulate is played by DNA-dependent protein kinase (DNA-PK) in mammals. Here we interrogate sites of MRN-dependent processing by identifying sites of CtIP association and by sequencing DNA-PK-bound DNA fragments that are products of MRN cleavage. These intermediates are generated most efficiently when DNA-PK is catalytically blocked, yielding products within 200 bp of the break site, whereas DNA-PK products in the absence of kinase inhibition show greater dispersal. Use of light-activated Cas9 to induce breaks facilitates temporal resolution of DNA-PK and Mre11 binding, showing that both complexes bind to DNA ends before release of DNA-PK-bound products. These results support a sequential model of double-strand break repair involving collaborative interactions between homologous and non-homologous repair complexes.

Indexed as

Cell NucleusDNA Breaks, Double-StrandedAnimalsDNA-Activated Protein KinaseDNA RepairMammalsProteolysisDNA-Activated Protein Kinase

Identifiers

PMID37717054
PMCPMC10505227
OpenAlexW4386801569

What OpenQuestion holds

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LicenceCC BY
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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.