Evidence map›Paper›PMID 16874298›Full record

ArticleThe EMBO journal2006

DNA-PK autophosphorylation facilitates Artemis endonuclease activity.

Aaron A Goodarzi, Yaping Yu, Enriqueta Riballo, Pauline Douglas, Sarah A Walker, Ruiqiong Ye, Christine Härer, Caterina Marchetti, Nick Morrice, Penny A Jeggo and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 177 papers.

0numbers the graph read from it
0cells of the map it votes in
177citing papers in PubMed
9.1field-weighted citation impact, top 1% 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

177 citing papers in PubMed, 319 citations in OpenAlex.

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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

117 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

11 authors at 3 institutions in 2 countries.

Aaron A GoodarziGenome Damage and Stability Centre, University of Sussex, East Sussex, UK.
Yaping Yu
Enriqueta Riballo
Pauline Douglas
Sarah A Walker
Ruiqiong Ye
Christine Härer
Caterina Marchetti
Nick Morrice
Penny A Jeggo
Susan P Lees-Miller
University of Sussex · GBUniversity of Calgary · CAMRC Protein Phosphorylation and Ubiquitylation Unit · GB

Funding

Medical Research Council G0500897
6 · The paper itself

Abstract

The Artemis nuclease is defective in radiosensitive severe combined immunodeficiency patients and is required for the repair of a subset of ionising radiation induced DNA double-strand breaks (DSBs) in an ATM and DNA-PK dependent process. Here, we show that Artemis phosphorylation by ATM and DNA-PK in vitro is primarily attributable to S503, S516 and S645 and demonstrate ATM dependent phosphorylation at serine 645 in vivo. However, analysis of multisite phosphorylation mutants of Artemis demonstrates that Artemis phosphorylation is dispensable for endonuclease activity in vitro and for DSB repair and V(D)J recombination in vivo. Importantly, DNA-dependent protein kinase catalytic subunit (DNA-PKcs) autophosphorylation at the T2609-T2647 cluster, in the presence of Ku and target DNA, is required for Artemis-mediated endonuclease activity. Moreover, autophosphorylated DNA-PKcs stably associates with Ku-bound DNA with large single-stranded overhangs until overhang cleavage by Artemis. We propose that autophosphorylation triggers conformational changes in DNA-PK that enhance Artemis cleavage at single-strand to double-strand DNA junctions. These findings demonstrate that DNA-PK autophosphorylation regulates Artemis access to DNA ends, providing insight into the mechanism of Artemis mediated DNA end processing.

Indexed as

DNA RepairCatalytic DomainDNADNA-Activated Protein KinaseDNA-Binding ProteinsDNA HelicasesDNA, Single-StrandedEndonucleasesHumansKu AutoantigenNuclear ProteinsPhosphorylationProtein ConformationRecombination, GeneticSerineDCLRE1C protein, humanDNADNA-Activated Protein KinaseDNA-Binding ProteinsDNA HelicasesDNA, Single-StrandedEndonucleasesKu AutoantigenNuclear ProteinsSerineXRCC5 protein, human

Identifiers

PMID16874298
PMCPMC1553186
OpenAlexW2121070277

What OpenQuestion holds

Textmetadata
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.