Evidence map›Paper›PMID 26990988›Full record

ArticleMolecular cell2016

Two-Stage Synapsis of DNA Ends during Non-homologous End Joining.

Thomas G W Graham, Johannes C Walter, Joseph J Loparo

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.

0numbers the graph read from it
0cells of the map it votes in
129citing papers in PubMed
8.5field-weighted citation impact, top 2% 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

129 citing papers in PubMed, 214 citations in OpenAlex.

  1. DNA Repair Mechanisms.Methods in molecular biology (Clifton, N.J.) · 2027
    Review
  2. Taming Mre11-Rad50 at Telomeres: Convergent Strategies for Chromosome-End Protection Across Evolution.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026
    Review
  3. Core NHEJ Factors Maintain Synapsis Across Diverse DNA End Structures.bioRxiv : the preprint server for biology · 2026
    Article
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69 more citing papers are in PubMed but not listed here.

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

3 authors at 2 institutions in 1 country.

Thomas G W GrahamDepartment of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Johannes C WalterDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA. Electronic address: johannes_walter@hms.harvard.edu.
Joseph J LoparoDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: joseph_loparo@hms.harvard.edu.
Harvard University · USHoward Hughes Medical Institute · US

Funding

Visualizing DNA break repair: single-molecule studies of non-homologous end joiningR01GM115487 · NIGMS · HARVARD MEDICAL SCHOOL · PI LOPARO, JOSEPH J. · 2015 to 2024
$3.1M
Howard Hughes Medical InstituteNCI NIH HHS BC120436NIGMS NIH HHS R01 GM115487NIGMS NIH HHS R01GM115487
6 · The paper itself

Abstract

Repair of DNA double-strand breaks (DSBs) is essential for genomic stability. The most common DSB repair mechanism in human cells, non-homologous end joining (NHEJ), rejoins broken DNA ends by direct ligation. It remains unclear how components of the NHEJ machinery assemble a synaptic complex that bridges DNA ends. Here, we use single-molecule imaging in a vertebrate cell-free extract to show that synapsis of DNA ends occurs in at least two stages that are controlled by different NHEJ factors. DNA ends are initially tethered in a long-range complex whose formation requires the Ku70/80 heterodimer and the DNA-dependent protein kinase catalytic subunit. The ends are then closely aligned, which requires XLF, a non-catalytic function of XRCC4-LIG4, and DNA-PK activity. These results reveal a structural transition in the synaptic complex that governs alignment of DNA ends. Our approach provides a means of studying physiological DNA DSB repair at single-molecule resolution.

Indexed as

Antigens, NuclearCell-Free SystemChromosome PairingDNA-Activated Protein KinaseDNA-Binding ProteinsDNA Breaks, Double-StrandedDNA End-Joining RepairDNA Ligase ATPDNA LigasesDNA RepairDNA Repair EnzymesHumansKu AutoantigenMolecular ImagingProtein BindingAntigens, NuclearDNA-Activated Protein KinaseDNA-Binding ProteinsDNA Ligase ATPDNA LigasesDNA Repair EnzymesKu AutoantigenLIG4 protein, humanNHEJ1 protein, humanXRCC4 protein, humanXrcc6 protein, human

Identifiers

PMID26990988
PMCPMC4799494
OpenAlexW2297808341

What OpenQuestion holds

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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.