Evidence map›Paper›PMID 24656613›Full record

ReviewDNA repair2014

Structural insights into NHEJ: building up an integrated picture of the dynamic DSB repair super complex, one component and interaction at a time.

Gareth J Williams, Michal Hammel, Sarvan Kumar Radhakrishnan, Dale Ramsden, Susan P Lees-Miller, John A Tainer

Open access · greenAbstract readReview
In one paragraph

Review in DNA repair, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed
7.5field-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

71 citing papers in PubMed, 113 citations in OpenAlex.

  1. Article
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  4. Frontiers in immunology · 2025
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  6. Review
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  13. Towards Personalized Management of Ovarian Cancer.Cancer management and research · 2022
    Review
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  15. Article
  16. Article
  17. Review
  18. Review
  19. Article
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11 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

6 authors at 4 institutions in 2 countries.

Gareth J WilliamsLife Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, United States.
Michal HammelPhysical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, United States.
Sarvan Kumar RadhakrishnanDepartment of Biochemistry & Molecular Biology, Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, T2 N 4N1 Canada.
Dale RamsdenLineberger Comprehensive Cancer Center, Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 2759, United States.
Susan P Lees-MillerDepartment of Biochemistry & Molecular Biology, Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, T2 N 4N1 Canada; Department of Oncology, Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, T2 N 4N1 Canada. Electronic address: leesmill@ucalgary.ca.
John A TainerLife Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, United States; Department of Molecular Biology, Skaggs Institute of Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, United States. Electronic address: jat@scripps.edu.
Lawrence Berkeley National Laboratory · USUniversity of Calgary · CAScripps Research Institute · USUniversity of North Carolina at Chapel Hill · US

Funding

Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI John A. Tainer · 2001 to 2026
$89.6M
Resolution of Complex Breaks by Nonhomologous End JoiningR01CA084442 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI RAMSDEN, DALE A · 2000 to 2019
$4.8M
DNA Polymerases in Nonhomologous End JoiningU01CA097096 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI RAMSDEN, DALE A · 2019 to 2022
$1.4M
NCI NIH HHS CA84442NCI NIH HHS P01 CA092584NCI NIH HHS P01 CA92584NCI NIH HHS R01 CA084442NCI NIH HHS U01 CA097096
6 · The paper itself

Abstract

Non-homologous end joining (NHEJ) is the major pathway for repair of DNA double-strand breaks (DSBs) in human cells. NHEJ is also needed for V(D)J recombination and the development of T and B cells in vertebrate immune systems, and acts in both the generation and prevention of non-homologous chromosomal translocations, a hallmark of genomic instability and many human cancers. X-ray crystal structures, cryo-electron microscopy envelopes, and small angle X-ray scattering (SAXS) solution conformations and assemblies are defining most of the core protein components for NHEJ: Ku70/Ku80 heterodimer; the DNA dependent protein kinase catalytic subunit (DNA-PKcs); the structure-specific endonuclease Artemis along with polynucleotide kinase/phosphatase (PNKP), aprataxin and PNKP related protein (APLF); the scaffolding proteins XRCC4 and XLF (XRCC4-like factor); DNA polymerases, and DNA ligase IV (Lig IV). The dynamic assembly of multi-protein NHEJ complexes at DSBs is regulated in part by protein phosphorylation. The basic steps of NHEJ have been biochemically defined to require: (1) DSB detection by the Ku heterodimer with subsequent DNA-PKcs tethering to form the DNA-PKcs-Ku-DNA complex (termed DNA-PK), (2) lesion processing, and (3) DNA end ligation by Lig IV, which functions in complex with XRCC4 and XLF. The current integration of structures by combined methods is resolving puzzles regarding the mechanisms, coordination and regulation of these three basic steps. Overall, structural results suggest the NHEJ system forms a flexing scaffold with the DNA-PKcs HEAT repeats acting as compressible macromolecular springs suitable to store and release conformational energy to apply forces to regulate NHEJ complexes and the DNA substrate for DNA end protection, processing, and ligation.

Indexed as

DNA Breaks, Double-StrandedDNA End-Joining RepairDNADNA Repair EnzymesHumansModels, MolecularMultienzyme ComplexesProtein ConformationDNADNA Repair EnzymesMultienzyme ComplexesMRNNHEJSAXSX-ray crystallography

Identifiers

PMID24656613
PMCPMC4102006
OpenAlexW2162593589

What OpenQuestion holds

Textmetadata
LicenceTDM
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.