Evidence map›Paper›PMID 30409670›Full record

ArticleDNA repair2019

Deciphering phenotypic variance in different models of DNA-PKcs deficiency.

Jessica A Neal, Katheryn Meek

Abstract read
In one paragraph

Article in DNA repair, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
0.7field-weighted citation impact, top 29% 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

15 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Secrets of DNA-PKcs beyond DNA repair.NPJ precision oncology · 2024
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. DNA-PKcs phosphorylation at the T2609 cluster alters the repair pathway choice during immunoglobulin class switch recombination.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  15. Article
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

2 authors at 1 institution in 1 country.

Jessica A NealCollege of Veterinary Medicine, Department of Microbiology & Molecular Genetics, and Department of Pathobiology & Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA.
Katheryn MeekCollege of Veterinary Medicine, Department of Microbiology & Molecular Genetics, and Department of Pathobiology & Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA. Electronic address: kmeek@msu.edu.
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
NIAID NIH HHS R01 AI048758
6 · The paper itself

Abstract

DNA-PKcs deficiency has been studied in numerous animal models and cell culture systems. In previous studies of kinase inactivating mutations in cell culture systems, ablation of DNA-PK's catalytic activity results in a cell phenotype that is virtually indistinguishable from that ascribed to complete loss of the enzyme. However, a recent compelling study demonstrates a remarkably more severe phenotype in mice harboring a targeted disruption of DNA-PK's ATP binding site as compared to DNA-PKcs deficient mice. Here we investigate the mechanism for these divergent results. We find that kinase inactivating DNA-PKcs mutants markedly radiosensitize immortalized DNA-PKcs deficient cells, but have no substantial effects on transformed DNA-PKcs deficient cells. Since the non-homologous end joining mechanism likely functions similarly in all of these cell strains, it seems unlikely that kinase inactive DNA-PK could impair the end joining mechanism in some cell types, but not in others. In fact, we observed no significant differences in either episomal or chromosomal end joining assays in cells expressing kinase inactivated DNA-PKcs versus no DNA-PKcs. Several potential explanations could explain these data including a non-catalytic role for DNA-PKcs in promoting cell death, or alteration of gene expression by loss of DNA-PKcs as opposed to inhibition of its catalytic activity. Finally, controversy exists as to whether DNA-PKcs autophosphorylates or is the target of other PIKKs; we present data demonstrating that DNA-PK primarily autophosphorylates.

Indexed as

PhenotypeAdenosine TriphosphateAnimalsDNA-Activated Protein KinaseDNA-Binding ProteinsDNA Breaks, Double-StrandedHCT116 CellsHumansMiceNuclear ProteinsPhosphorylationAdenosine TriphosphateDNA-Activated Protein KinaseDNA-Binding ProteinsNuclear ProteinsPRKDC protein, humanPrkdc protein, mouseDNA dependent protein kinaseDNA-PKcsNon-homologous end joining (NHEJ)

Identifiers

PMID30409670
PMCPMC6312468
OpenAlexW2899115543

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.