Evidence map›Paper›PMID 26130724›Full record

ArticleNucleic acids research2015

Human DNA ligase III bridges two DNA ends to promote specific intermolecular DNA end joining.

Vandna Kukshal, In-Kwon Kim, Gregory L Hura, Alan E Tomkinson, John A Tainer, Tom Ellenberger

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2015. 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
1.7field-weighted citation impact, top 17% 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, 26 citations in OpenAlex.

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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 1 country.

Vandna KukshalDepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Saint Louis, MO 63110, USA.
In-Kwon KimDepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Gregory L HuraLife Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Alan E TomkinsonDepartment of Internal Medicine and University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM 87131, USA.
John A TainerLife Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Tom EllenbergerDepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Saint Louis, MO 63110, USA tome@biochem.wustl.edu.
Washington University in St. Louis · USLawrence Berkeley National Laboratory · USNew Mexico Cancer Center · USThe University of Texas MD Anderson Cancer Center · US

Funding

Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI John A. Tainer · 2001 to 2026
$89.6M
Roles of LIG3 and XRCC1 genes in genome stability.R01ES012512 · NIEHS · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI Alan E Tomkinson · 2004 to 2026
$6.3M
NCI NIH HHS P01 CA092584NIEHS NIH HHS R01 ES012512NIGMS NIH HHS GM052504
6 · The paper itself

Abstract

Mammalian DNA ligase III (LigIII) functions in both nuclear and mitochondrial DNA metabolism. In the nucleus, LigIII has functional redundancy with DNA ligase I whereas LigIII is the only mitochondrial DNA ligase and is essential for the survival of cells dependent upon oxidative respiration. The unique LigIII zinc finger (ZnF) domain is not required for catalytic activity but senses DNA strand breaks and stimulates intermolecular ligation of two DNAs by an unknown mechanism. Consistent with this activity, LigIII acts in an alternative pathway of DNA double strand break repair that buttresses canonical non-homologous end joining (NHEJ) and is manifest in NHEJ-defective cancer cells, but how LigIII acts in joining intermolecular DNA ends versus nick ligation is unclear. To investigate how LigIII efficiently joins two DNAs, we developed a real-time, fluorescence-based assay of DNA bridging suitable for high-throughput screening. On a nicked duplex DNA substrate, the results reveal binding competition between the ZnF and the oligonucleotide/oligosaccharide-binding domain, one of three domains constituting the LigIII catalytic core. In contrast, these domains collaborate and are essential for formation of a DNA-bridging intermediate by adenylated LigIII that positions a pair of blunt-ended duplex DNAs for efficient and specific intermolecular ligation.

Indexed as

DNA End-Joining RepairDNADNA Ligase ATPDNA LigasesHumansModels, MolecularPoly-ADP-Ribose Binding ProteinsProtein BindingProtein Structure, TertiaryXenopus ProteinsZinc FingersDNADNA Ligase ATPDNA ligase III alpha protein, XenopusDNA LigasesLIG3 protein, humanPoly-ADP-Ribose Binding ProteinsXenopus Proteins

Identifiers

PMID26130724
PMCPMC4538836
OpenAlexW1680622557

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.