Evidence map›Paper›PMID 26941327›Full record

ArticleMolecular biology of the cell2016

Unique epigenetic influence of H2AX phosphorylation and H3K56 acetylation on normal stem cell radioresponses.

Keith M Jacobs, Sandeep Misri, Barbara Meyer, Suyash Raj, Cheri L Zobel, Barry P Sleckman, Dennis E Hallahan, Girdhar G Sharma

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

16 citing papers in PubMed, 28 citations in OpenAlex.

  1. Review
  2. Effects of dopamine receptor antagonists and radiation on mouse neural stem/progenitor cells.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2024
    Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Mesenchymal Stem Cells Early Response to Low-Dose Ionizing Radiation.Frontiers in cell and developmental biology · 2020
    Article
  10. Article
  11. When epigenetics meets bioengineering-A material characteristics and surface topography perspective.Journal of biomedical materials research. Part B, Applied biomaterials · 2018
    Review
  12. Article
  13. Review
  14. Review
  15. Molecular Pathogenesis of Radiation-Induced Cell Toxicity in Stem Cells.International journal of molecular sciences · 2017
    Review
  16. 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

8 authors at 1 institution in 1 country.

Keith M JacobsDepartment of Radiation Oncology, Cancer Biology Division, Washington University School of Medicine, St. Louis, MO 63108.
Sandeep MisriDepartment of Radiation Oncology, Cancer Biology Division, Washington University School of Medicine, St. Louis, MO 63108.
Barbara MeyerDepartment of Radiation Oncology, Cancer Biology Division, Washington University School of Medicine, St. Louis, MO 63108.
Suyash RajDepartment of Radiation Oncology, Cancer Biology Division, Washington University School of Medicine, St. Louis, MO 63108.
Cheri L ZobelDepartment of Radiation Oncology, Cancer Biology Division, Washington University School of Medicine, St. Louis, MO 63108.
Barry P SleckmanSiteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63108 Department of Pathology, Laboratory and Genomic Medicine, Washington University School of Medicine, St. Louis, MO 63108.
Dennis E HallahanDepartment of Radiation Oncology, Cancer Biology Division, Washington University School of Medicine, St. Louis, MO 63108 Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63108.
Girdhar G SharmaDepartment of Radiation Oncology, Cancer Biology Division, Washington University School of Medicine, St. Louis, MO 63108 Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63108 sharma@wustl.edu.
Washington University in St. Louis · US

Funding

ATM FUNCTION DURING V(D)J RECOMBINATIONR01AI074953 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI SLECKMAN, BARRY P · 2009 to 2023
$5.9M
THE ROLE OF PROTEIN PHOSPHATASE PP2A IN RADIATION INDUCED STEM CELL APOPTOSISR01CA174966 · NCI · WASHINGTON UNIVERSITY · PI HALLAHAN, DENNIS E, SHARMA, GIRDHAR GOPAL · 2013 to 2017
$2.3M
NCI NIH HHS R01 CA174966NCI NIH HHS R01CA174966NIAID NIH HHS R01 AI074953
6 · The paper itself

Abstract

Normal tissue injury resulting from cancer radiotherapy is often associated with diminished regenerative capacity. We examined the relative radiosensitivity of normal stem cell populations compared with non-stem cells within several radiosensitive tissue niches and culture models. We found that these stem cells are highly radiosensitive, in contrast to their isogenic differentiated progeny. Of interest, they also exhibited a uniquely attenuated DNA damage response (DDR) and muted DNA repair. Whereas stem cells exhibit reduced ATM activation and ionizing radiation-induced foci, they display apoptotic pannuclear H2AX-S139 phosphorylation (γH2AX), indicating unique radioresponses. We also observed persistent phosphorylation of H2AX-Y142 along the DNA breaks in stem cells, which promotes apoptosis while inhibiting DDR signaling. In addition, down-regulation of constitutively elevated histone-3 lysine-56 acetylation (H3K56ac) in stem cells significantly decreased their radiosensitivity, restored DDR function, and increased survival, signifying its role as a key contributor to stem cell radiosensitivity. These results establish that unique epigenetic landscapes affect cellular heterogeneity in radiosensitivity and demonstrate the nonubiquitous nature of radiation responses. We thus elucidate novel epigenetic rheostats that promote ionizing radiation hypersensitivity in various normal stem cell populations, identifying potential molecular targets for pharmacological radioprotection of stem cells and hopefully improving the efficacy of future cancer treatment.

Indexed as

AcetylationAnimalsApoptosisAtaxia Telangiectasia Mutated ProteinsDNA DamageDNA RepairDown-RegulationEpigenesis, GeneticHepatocyte Growth FactorHistonesLysineMaleMice, Inbred C57BLPhosphorylationProto-Oncogene ProteinsRadiation, IonizingAtaxia Telangiectasia Mutated ProteinsAtm protein, mousegamma-H2AX protein, mouseHepatocyte Growth FactorHistonesLysinemacrophage stimulating proteinProto-Oncogene Proteins

Identifiers

PMID26941327
PMCPMC4831886
OpenAlexW2332766086

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.