Evidence map›Paper›PMID 25012654›Full record

ArticleThe Journal of biological chemistry2014

Human pluripotent stem cells have a novel mismatch repair-dependent damage response.

Bo Lin, Dipika Gupta, Christopher D Heinen

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.6field-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

22 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
  2. Article
  3. Prime Editing in Dividing and Quiescent Cells.International journal of molecular sciences · 2025
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. DNA repair fidelity in stem cell maintenance, health, and disease.Biochimica et biophysica acta. Molecular basis of disease · 2020
    Review
  12. Article
  13. Article
  14. ATR-Chk1 activation mitigates replication stress caused by mismatch repair-dependent processing of DNA damage.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  15. Review
  16. Article
  17. Review
  18. Mitochondria in human pluripotent stem cell apoptosis.Seminars in cell & developmental biology · 2016
    Review
  19. Review
  20. Stem cells: the pursuit of genomic stability.International journal of molecular sciences · 2014
    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

3 authors at 1 institution in 1 country.

Bo LinFrom the Center for Molecular Medicine and Neag Comprehensive Cancer Center, University of Connecticut Health Center, Farmington, Connecticut 06030-3101.
Dipika GuptaFrom the Center for Molecular Medicine and Neag Comprehensive Cancer Center, University of Connecticut Health Center, Farmington, Connecticut 06030-3101.
Christopher D HeinenFrom the Center for Molecular Medicine and Neag Comprehensive Cancer Center, University of Connecticut Health Center, Farmington, Connecticut 06030-3101 cheinen@uchc.edu.
UConn Health · US

Funding

Mismatch Repair Functions Affected During TumorigenesisR01CA115783 · NCI · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI HEINEN, CHRISTOPHER D. · 2008 to 2012
$1.2M
NCI NIH HHS CA115783NCI NIH HHS R01 CA115783
6 · The paper itself

Abstract

Human pluripotent stem cells (PSCs) are presumed to have robust DNA repair pathways to ensure genome stability. PSCs likely need to protect against mutations that would otherwise be propagated throughout all tissues of the developing embryo. How these cells respond to genotoxic stress has only recently begun to be investigated. Although PSCs appear to respond to certain forms of damage more efficiently than somatic cells, some DNA damage response pathways such as the replication stress response may be lacking. Not all DNA repair pathways, including the DNA mismatch repair (MMR) pathway, have been well characterized in PSCs to date. MMR maintains genomic stability by repairing DNA polymerase errors. MMR is also involved in the induction of cell cycle arrest and apoptosis in response to certain exogenous DNA-damaging agents. Here, we examined MMR function in PSCs. We have demonstrated that PSCs contain a robust MMR pathway and are highly sensitive to DNA alkylation damage in an MMR-dependent manner. Interestingly, the nature of this alkylation response differs from that previously reported in somatic cell types. In somatic cells, a permanent G2/M cell cycle arrest is induced in the second cell cycle after DNA damage. The PSCs, however, directly undergo apoptosis in the first cell cycle. This response reveals that PSCs rely on apoptotic cell death as an important defense to avoid mutation accumulation. Our results also suggest an alternative molecular mechanism by which the MMR pathway can induce a response to DNA damage that may have implications for tumorigenesis.

Indexed as

Base Pair MismatchDNA DamageDNA RepairApoptosisCell CycleCells, CulturedHumansInduced Pluripotent Stem CellsMethylnitronitrosoguanidineMethylnitronitrosoguanidineApoptosisDNA Damage ResponseDNA Mismatch RepairDNA RepairEmbryonic Stem CellInduced Pluripotent Stem CellsPluripotent Stem Cells

Identifiers

PMID25012654
PMCPMC4148860
OpenAlexW2007701240

What OpenQuestion holds

Textmetadata
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.