Evidence map›Paper›PMID 31399561›Full record

ArticleNature communications2019

The essential elements for the noncovalent association of two DNA ends during NHEJ synapsis.

Bailin Zhao, Go Watanabe, Michael J Morten, Dylan A Reid, Eli Rothenberg, Michael R Lieber

Abstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing 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

66 citing papers in PubMed.

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  20. Phosphorylation of DNA-PKcs at the S2056 cluster ensures efficient and productive lymphocyte development in XLF-deficient mice.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article

6 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.

Bailin ZhaoDepartment of Pathology, Department of Biochemistry & Molecular Biology, Department of Molecular Microbiology & Immunology, and Section of Computational & Molecular Biology, USC Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA, 90089, USA.ORCID http://orcid.org/0000-0001-5894-0079
Go WatanabeDepartment of Pathology, Department of Biochemistry & Molecular Biology, Department of Molecular Microbiology & Immunology, and Section of Computational & Molecular Biology, USC Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA, 90089, USA.ORCID http://orcid.org/0000-0003-3911-3021
Michael J MortenDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, 10016, USA.
Dylan A ReidDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, 10016, USA.
Eli RothenbergDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, 10016, USA. eli.rothenberg@nyumc.org.
Michael R LieberDepartment of Pathology, Department of Biochemistry & Molecular Biology, Department of Molecular Microbiology & Immunology, and Section of Computational & Molecular Biology, USC Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA, 90089, USA. lieber@usc.edu.

Funding

MECHANISM AND REGULATION OF NONHOMOLOGOUS DNA ENDJOININGR01CA100504 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI LIEBER, MICHAEL R · 2003 to 2021
$5.0M
Site-Specific Recombination in Human Health & DiseaseR35GM118009 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI LIEBER, MICHAEL R · 2016 to 2025
$4.4M
Mechanisms of Human Lymphoid Chromosomal TranslocationR01CA196671 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI LIEBER, MICHAEL R · 2016 to 2021
$1.9M
Single-Molecule Studies of Non-Homologous DNA End JoiningR01GM108119 · NIGMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ROTHENBERG, ELI · 2015 to 2019
$1.7M
NCI NIH HHS R01 CA100504NCI NIH HHS R01 CA196671NIGMS NIH HHS R01 GM108119NIGMS NIH HHS R35 GM118009
6 · The paper itself

Abstract

One of the most central questions about the repair of a double-strand DNA break (DSB) concerns how the two free DNA ends are brought together - a step called synapsis. Using single-molecule FRET (smFRET), we show here that both Ku plus XRCC4:DNA ligase IV are necessary and sufficient to achieve a flexible synapsis of blunt DNA ends, whereas either alone is not. Addition of XLF causes a transition to a close synaptic state, and maximum efficiency of close synapsis is achieved within 20 min. The promotion of close synapsis by XLF indicates a role that is independent of a filament structure, with action focused at the very ends of each duplex. DNA-PKcs is not required for the formation of either the flexible or close synaptic states. This model explains in biochemical terms the evolutionarily central synaptic role of Ku, X4L4, and XLF in NHEJ for all eukaryotes.

Indexed as

DNA Breaks, Double-StrandedDNA End-Joining RepairDNA-Binding ProteinsDNA Ligase ATPDNA Repair EnzymesFluorescence Resonance Energy TransferKu AutoantigenModels, GeneticRecombinant ProteinsSingle Molecule ImagingDNA-Binding ProteinsDNA Ligase ATPDNA Repair EnzymesKu AutoantigenLIG4 protein, humanNHEJ1 protein, humanRecombinant ProteinsXRCC4 protein, humanXRCC5 protein, human

Identifiers

PMID31399561
PMCPMC6688983

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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.