Evidence map›Paper›PMID 20844317›Full record

ArticleAging2010

ATM-independent, high-fidelity nonhomologous end joining predominates in human embryonic stem cells.

Bret R Adams, Amy J Hawkins, Lawrence F Povirk, Kristoffer Valerie

Open access · hybridAbstract read
In one paragraph

Article in Aging, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.8field-weighted citation impact, top 6% 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

32 citing papers in PubMed, 57 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Cycling to Meet Fate: Connecting Pluripotency to the Cell Cycle.Frontiers in cell and developmental biology · 2018
    Review
  6. Article
  7. DNA repair mechanisms in embryonic stem cells.Cellular and molecular life sciences : CMLS · 2017
    Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Stem cells: the pursuit of genomic stability.International journal of molecular sciences · 2014
    Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. 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

4 authors at 1 institution in 1 country.

Bret R AdamsDepartment of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
Amy J Hawkins
Lawrence F Povirk
Kristoffer Valerie
Virginia Commonwealth University · US

Funding

Virus Vector Shared ResourceP30CA016059 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI Keri R Maher · 1985 to 2026
$51.0M
Repair of DNA double-strand breaks with damaged endsR01CA040615 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI POVIRK, LAWRENCE F · 1985 to 2014
$3.2M
ATM as target for malignant glioma radiosensitization.R01NS064593 · NINDS · VIRGINIA COMMONWEALTH UNIVERSITY · PI VALERIE, KRISTOFFER CARL · 2009 to 2013
$1.7M
NCI NIH HHS P30 CA016059NCI NIH HHS P30CA16059NCI NIH HHS R01 CA040615NINDS NIH HHS R01 NS064593
6 · The paper itself

Abstract

We recently demonstrated that human embryonic stem cells (hESCs) utilize homologous recombination repair (HRR) as primary means of double-strand break (DSB) repair. We now show that hESCs also use nonhomologous end joining (NHEJ). NHEJ kinetics were several-fold slower in hESCs and neural progenitors (NPs) than in astrocytes derived from hESCs. ATM and DNA-PKcs inhibitors were ineffective or partially effective, respectively, at inhibiting NHEJ in hESCs, whereas progressively more inhibition was seen in NPs and astrocytes. The lack of any major involvement of DNA-PKcs in NHEJ in hESCs was supported by siRNA-mediated DNA-PKcs knockdown. Expression of a truncated XRCC4 decoy or XRCC4 knock-down reduced NHEJ by more than half suggesting that repair is primarily canonical NHEJ. Poly(ADP-ribose) polymerase (PARP) was dispensable for NHEJ suggesting that repair is largely independent of backup NHEJ. Furthermore, as hESCs differentiated a progressive decrease in the accuracy of NHEJ was observed. Altogether, we conclude that NHEJ in hESCs is largely independent of ATM, DNA-PKcs, and PARP but dependent on XRCC4 with repair fidelity several-fold greater than in astrocytes.

Indexed as

DNAAstrocytesAtaxia Telangiectasia Mutated ProteinsBase SequenceCell Cycle ProteinsCell DifferentiationCells, CulturedDNA-Binding ProteinsDNA RepairDNA Repair EnzymesEmbryonic Stem CellsHumansMolecular Sequence DataPoly(ADP-ribose) PolymerasesProtein Kinase CProtein Serine-Threonine KinasesAtaxia Telangiectasia Mutated ProteinsATM protein, humanCell Cycle ProteinsDNADNA-Binding ProteinsDNA Repair EnzymesNHEJ1 protein, humanPoly(ADP-ribose) PolymerasesProtein Kinase CProtein Serine-Threonine KinasesTumor Suppressor ProteinsXRCC4 protein, human

Identifiers

PMID20844317
PMCPMC2984607
OpenAlexW1269552450

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.