Evidence map›Paper›PMID 32716029›Full record

ArticleNucleic acids research2020

Activation of DNA-PK by hairpinned DNA ends reveals a stepwise mechanism of kinase activation.

Katheryn Meek

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

23 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. ER-associated degradation ligase HRD1 links ER stress to DNA damage repair by modulating the activity of DNA-PKcs.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  3. Review
  4. Secrets of DNA-PKcs beyond DNA repair.NPJ precision oncology · 2024
    Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Targeting DNA-PK.Cancer treatment and research · 2023
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Review
  20. Review
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

1 author at 1 institution in 1 country.

Katheryn MeekDepartment of Microbiology & Molecular Genetics, and Department of Pathobiology & Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.
Michigan State University · US

Funding

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
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
NCI NIH HHS R21 CA240875NIAID NIH HHS R01 AI048758NIAID NIH HHS R01 AI147634
6 · The paper itself

Abstract

As its name implies, the DNA dependent protein kinase (DNA-PK) requires DNA double-stranded ends for enzymatic activation. Here, I demonstrate that hairpinned DNA ends are ineffective for activating the kinase toward many of its well-studied substrates (p53, XRCC4, XLF, HSP90). However, hairpinned DNA ends robustly stimulate certain DNA-PK autophosphorylations. Specifically, autophosphorylation sites within the ABCDE cluster are robustly phosphorylated when DNA-PK is activated by hairpinned DNA ends. Of note, phosphorylation of the ABCDE sites is requisite for activation of the Artemis nuclease that associates with DNA-PK to mediate hairpin opening. This finding suggests a multi-step mechanism of kinase activation. Finally, I find that all non-homologous end joining (NHEJ) defective cells (whether deficient in components of the DNA-PK complex or components of the ligase complex) are similarly deficient in joining DNA double-stranded breaks (DSBs) with hairpinned termini.

Indexed as

DNADNA-Activated Protein KinaseDNA-Binding ProteinsDNA Breaks, Double-StrandedDNA End-Joining RepairDNA LigasesDNA RepairDNA Repair EnzymesHSP90 Heat-Shock ProteinsHumansPhosphorylationProtein BindingTumor Suppressor Protein p53DNADNA-Activated Protein KinaseDNA-Binding ProteinsDNA LigasesDNA Repair EnzymesHSP90 Heat-Shock ProteinsNHEJ1 protein, humanTumor Suppressor Protein p53XRCC4 protein, human

Identifiers

PMID32716029
PMCPMC7498359
OpenAlexW3045519633

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.