Evidence map›Paper›PMID 26276388›Full record

ArticleThe Journal of biological chemistry2015

Unifying the DNA end-processing roles of the artemis nuclease: Ku-dependent artemis resection at blunt DNA ends.

Howard H Y Chang, Go Watanabe, Michael R Lieber

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing 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

36 citing papers in PubMed.

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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

3 authors.

Howard H Y ChangFrom the Departments of Pathology, Biochemistry and Molecular Biology, Biological Sciences, and Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles, California.
Go WatanabeFrom the Departments of Pathology, Biochemistry and Molecular Biology, Biological Sciences, and Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles, California.
Michael R LieberFrom the Departments of Pathology, Biochemistry and Molecular Biology, Biological Sciences, and Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles, California 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
NCI NIH HHS R01 CA100504NCI NIH HHS R01 CA196671NIGMS NIH HHS R35 GM118009
6 · The paper itself

Abstract

Artemis is a member of the metallo-β-lactamase protein family of nucleases. It is essential in vertebrates because, during V(D)J recombination, the RAG complex generates hairpins when it creates the double strand breaks at V, D, and J segments, and Artemis is required to open the hairpins so that they can be joined. Artemis is a diverse endo- and exonuclease, and creating a unified model for its wide range of nuclease properties has been challenging. Here we show that Artemis resects iteratively into blunt DNA ends with an efficiency that reflects the AT-richness of the DNA end. GC-rich ends are not cut by Artemis alone because of a requirement for DNA end breathing (and confirmed using fixed pseudo-Y structures). All DNA ends are cut when both the DNA-dependent protein kinase catalytic subunit and Ku accompany Artemis but not when Ku is omitted. These are the first biochemical data demonstrating a Ku dependence of Artemis action on DNA ends of any configuration. The action of Artemis at blunt DNA ends is slower than at overhangs, consistent with a requirement for a slow DNA end breathing step preceding the cut. The AT sequence dependence, the order of strand cutting, the length of the cuts, and the Ku-dependence of Artemis action at blunt ends can be reconciled with the other nucleolytic properties of both Artemis and Artemis·DNA-PKcs in a model incorporating DNA end breathing of blunt ends to form transient single to double strand boundaries that have structural similarities to hairpins and fixed 5' and 3' overhangs.

Indexed as

Adenosine TriphosphateCatalysisDNADNA-Activated Protein KinaseDNA-Binding ProteinsDNA DamageDNA HelicasesDNA RepairDNA, Single-StrandedEndonucleasesHumansKu AutoantigenNuclear ProteinsOligonucleotidesProtein BindingV(D)J RecombinationAdenosine TriphosphateDCLRE1C protein, humanDNADNA-Activated Protein KinaseDNA-Binding ProteinsDNA HelicasesDNA, Single-StrandedEndonucleasesKu AutoantigenNuclear ProteinsOligonucleotidesPRKDC protein, humanXRCC5 protein, humanDNADNA binding proteinDNA endonucleaseDNA enzymeDNA repairendonuclease

Identifiers

PMID26276388
PMCPMC4591795

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.