Evidence map›Paper›PMID 34936881›Full record

ArticleMolecular cell2022

Autophosphorylation transforms DNA-PK from protecting to processing DNA ends.

Lan Liu, Xuemin Chen, Jun Li, Huaibin Wang, Christopher J Buehl, Noah J Goff, Katheryn Meek, Wei Yang, Martin Gellert

Open access · greenAbstract readVideo-Audio Media
In one paragraph

Article in Molecular cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
5.1field-weighted citation impact, top 3% 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

60 citing papers in PubMed, 81 citations in OpenAlex.

  1. Review
  2. Article
  3. Core NHEJ Factors Maintain Synapsis Across Diverse DNA End Structures.bioRxiv : the preprint server for biology · 2026
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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

9 authors at 2 institutions in 1 country.

Lan LiuLaboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
Xuemin ChenLaboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
Jun LiLaboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
Huaibin WangLaboratory of Cell and Molecular Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
Christopher J BuehlDepartment of Microbiology and Molecular Genetics, and Department of Pathology & Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.
Noah J GoffDepartment of Microbiology and Molecular Genetics, and Department of Pathology & Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.
Katheryn MeekDepartment of Microbiology and Molecular Genetics, and Department of Pathology & Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA. Electronic address: kmeek@msu.edu.
Wei YangLaboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: weiy@niddk.nih.gov.
Martin GellertLaboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: martinge@niddk.nih.gov.
National Institutes of Health · USMichigan State University · US

Funding

Structural studies of the post-cleavage complex in V(D)J recombinationZIADK036167 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI GELLERT, MARTIN F. · 2009 to 2025
$21.4M
Structural and mechanistic studies of V(D)J recombinationZIADK036147 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI YANG, WEI · 2009 to 2025
$6.6M
Relevant Targets of the DNA Dependent Protein KinaseR01AI048758 · NIAID · MICHIGAN STATE UNIVERSITY · PI MEEK, KATHERYN D · 2000 to 2016
$5.2M
Defining the mechanistic basis of ATM’s impact on VDJ recombinationR01AI147634 · NIAID · MICHIGAN STATE UNIVERSITY · PI MEEK, KATHERYN D, YU, KEFEI · 2019 to 2024
$1.9M
The post-cleavage complex in V(D)J recombinationZ01DK036167 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI GELLERT, MARTIN F. · 2007 to 2008
$1.1M
Structural and mechanistic studies of RNase H and HIV reverse transcriptaseZ01DK036144 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI YANG, WEI · 2007 to 2008
$601k
Structural and mechanistic studies of V(D)J recombinationZ01DK036147 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI YANG, WEI · 2007 to 2008
$601k
Does overexpression of DNA polymerase theta sensitize cancers to G-quadruplex binding drugs?R21CA240875 · NCI · MICHIGAN STATE UNIVERSITY · PI MEEK, KATHERYN D · 2019 to 2020
$371k
Intramural NIH HHS Z01 DK036144Intramural NIH HHS Z01 DK036147Intramural NIH HHS Z01 DK036167NCI NIH HHS R21 CA240875NIAID NIH HHS R01 AI048758NIAID NIH HHS R01 AI147634
6 · The paper itself

Abstract

The DNA-dependent protein kinase (DNA-PK) initially protects broken DNA ends but then promotes their processing during non-homologous end joining (NHEJ). Before ligation by NHEJ, DNA hairpin ends generated during V(D)J recombination must be opened by the Artemis nuclease, together with autophosphorylated DNA-PK. Structures of DNA-PK bound to DNA before and after phosphorylation, and in complex with Artemis and a DNA hairpin, reveal an essential functional switch. When bound to open DNA ends in its protection mode, DNA-PK is inhibited for cis-autophosphorylation of the so-called ABCDE cluster but activated for phosphorylation of other targets. In contrast, DNA hairpin ends promote cis-autophosphorylation. Phosphorylation of four Thr residues in ABCDE leads to gross structural rearrangement of DNA-PK, widening the DNA binding groove for Artemis recruitment and hairpin cleavage. Meanwhile, Artemis locks DNA-PK into the kinase-inactive state. Kinase activity and autophosphorylation of DNA-PK are regulated by different DNA ends, feeding forward to coordinate NHEJ events.

Indexed as

DNA DamageDNA End-Joining RepairDNA-Activated Protein KinaseDNA-Binding ProteinsDNA, NeoplasmEndonucleasesEnzyme ActivationFemaleHEK293 CellsHeLa CellsHumansKu AutoantigenNucleic Acid ConformationPhosphorylationProtein BindingUterine Cervical NeoplasmsDCLRE1C protein, humanDNA-Activated Protein KinaseDNA-Binding ProteinsDNA, NeoplasmEndonucleasesKu AutoantigenPRKDC protein, humanXRCC5 protein, humanXrcc6 protein, humanArtemisDNA-PKcshairpinKu70Ku80NHEJSCIDV(D)J recombination

Identifiers

PMID34936881
PMCPMC8916119
OpenAlexW4200540683

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.