Evidence map›Paper›PMID 41285786›Full record

ArticleNature communications2025

Nonhomologous end-joining uses distinct mechanisms to repair each strand of a double strand break.

Adam J Luthman, Kishore K Chiruvella, Andrea M Kaminski, Thomas A Kunkel, Lars C Pedersen, Dale A Ramsden

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. 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.

Adam J Luthman *Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Kishore K Chiruvella *Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Andrea M KaminskiGenome Integrity and Structural Biology Laboratory, National Institutes of Environmental Health Sciences, 111 TW Alexander Drive, Durham, NC, USA.ORCID http://orcid.org/0000-0002-6263-4186
Thomas A KunkelGenome Integrity and Structural Biology Laboratory, National Institutes of Environmental Health Sciences, 111 TW Alexander Drive, Durham, NC, USA.ORCID http://orcid.org/0000-0002-9900-1788
Lars C PedersenGenome Integrity and Structural Biology Laboratory, National Institutes of Environmental Health Sciences, 111 TW Alexander Drive, Durham, NC, USA.ORCID http://orcid.org/0000-0002-4488-4077
Dale A RamsdenDepartment of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. dale_ramsden@med.unc.edu.ORCID http://orcid.org/0000-0003-1575-4748

Funding

Structural determinants of Pol theta functionP01CA247773 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Gaorav P. Gupta · 2020 to 2026
$15.2M
Crystallographic studies of macromolecular structuresZICES102645 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI PEDERSEN, LARS · 2018 to 2025
$12.6M
The Role of DNA Synthesis in Nonhomologous End JoiningR01CA097096 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DALE A RAMSDEN · 2003 to 2026
$5.5M
Structure-Function Studies Of DNA Replication FidelityZ01ES065070 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI KUNKEL, THOMAS A · 1991 to 2008
$4.3M
Intramural NIH HHS Z01 ES065070Intramural NIH HHS ZIC ES102645NCI NIH HHS P01 CA247773NCI NIH HHS R01 CA097096U.S. Department of Energy (DOE) KP1605010U.S. Department of Health & Human Services | National Institutes of Health (NIH) 1ZIC ES102645U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) P30M133893
6 · The paper itself

Abstract

Nonhomologous end-joining repairs chromosomal double strand breaks, but it is unknown whether both strands are repaired by this pathway, and if one strand break's repair path impacts the other. Here, we show that nonhomologous end-joining employs both of two a priori possible strategies. Strand breaks that can be directly ligated are joined near-simultaneously, with no effect of one strand break's repair path on the other. More complex end structures require obligatorily ordered repair. The first strand to be repaired is used as template for repair of the opposite/second strand break, with the latter repair reaction occurring fastest when also coupled to nonhomologous end-joining. Enforced asymmetry in repair of each strand break can extend to the gap-filling polymerase employed, and whether the polymerases incorporate RNA or DNA. Our results resolve questions about pathway mechanism and identify a requirement for flexibility of the nonhomologous end-joining machinery for efficient repair of both strand breaks within diverse cellular double strand breaks.

Indexed as

DNA Breaks, Double-StrandedDNA End-Joining RepairDNAHumansDNA

Identifiers

PMID41285786
PMCPMC12748747

What OpenQuestion holds

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Registered trials

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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.