Evidence map›Paper›PMID 22544226›Full record

ArticleChromosoma2012

HMGB1 gene knockout in mouse embryonic fibroblasts results in reduced telomerase activity and telomere dysfunction.

Eva Polanská, Zuzana Dobšáková, Martina Dvořáčková, Jiří Fajkus, Michal Štros

Abstract read
PubMed Publisher
In one paragraph

Article in Chromosoma, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 2 pooled it
3.2field-weighted citation impact, top 8% 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

40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 77 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. The Altered Functions of Shelterin Components in ALT Cells.International journal of molecular sciences · 2023
    Review
  10. Reliable Hallmarks and Biomarkers of Senescent Lymphocytes.International journal of molecular sciences · 2023
    Review
  11. Article
  12. Review
  13. Review
  14. Role of high-mobility group box 1 in cancer.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2022
    Article
  15. Review
  16. PfHMGB2 has a role in malaria parasite mosquito infection.Frontiers in cellular and infection microbiology · 2022
    Article
  17. Article
  18. Review
  19. Targeting HMGB3/hTERT axis for radioresistance in cervical cancer.Journal of experimental & clinical cancer research : CR · 2020
    Article
  20. Functional Diversity of Non-Histone Chromosomal Protein HmgB1.International journal of molecular sciences · 2020
    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

5 authors at 3 institutions in 1 country.

Eva PolanskáAcademy of Sciences of the Czech Republic, Institute of Biophysics, Brno, Czech Republic.
Zuzana Dobšáková
Martina Dvořáčková
Jiří Fajkus
Michal Štros
Czech Academy of Sciences, Institute of Biophysics · CZCentral European Institute of Technology · CZCentral European Institute of Technology – Masaryk University · CZ

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Telomere repeats are added onto chromosome ends by telomerase, consisting of two main core components: a catalytic protein subunit (telomerase reverse trancriptase, TERT), and an RNA subunit (telomerase RNA, TR). Here, we report for the first time evidence that HMGB1 (a chromatin-associated protein in mammals, acting as a DNA chaperone in transcription, replication, recombination, and repair) can modulate cellular activity of mammalian telomerase. Knockout of the HMGB1 gene (HMGB1 KO) in mouse embryonic fibroblasts (MEFs) results in chromosomal abnormalities, enhanced colocalization of γ-H2AX foci at telomeres, and a moderate shortening of telomere lengths. HMGB1 KO MEFs also exhibit significantly (>5-fold) lower telomerase activity than the wild-type MEFs. Correspondingly, enhanced telomerase activity is observed upon overexpression of HMGB1 in MEFs. HMGB1 physically interacts with both TERT and TR, as well as with active telomerase complex in vitro. However, direct interaction of HMGB1 with telomerase is most likely not accountable for the observed higher telomerase activity in HMGB1-containing cells, as revealed from the inability of purified HMGB1 protein to stimulate telomerase activity in vitro. While no transcriptional silencing of TERT is observed in HMGB1 KO MEFs, levels of TR are diminished (~3-fold), providing possible explanation for the observed lower telomerase activity in HMGB1 KO cells. Interestingly, knockout of the HMGB2 gene elevates telomerase activity (~3-fold) in MEFs, suggesting that the two closely related proteins of the HMGB family, HMGB1 and HMGB2, have opposite effects on telomerase activity in the cell. The ability of HMGB1 to modulate cellular activity of telomerase and to maintain telomere integrity can help to understand some aspects of the protein involvement in chromosome stability and cancer.

Indexed as

Gene Knockout TechniquesAnimalsCell LineChromosome AberrationsDNA DamageDNA FragmentationDNA ReplicationDown-RegulationFibroblastsHistonesHMGB1 ProteinHMGB2 ProteinIn Situ Hybridization, FluorescenceMiceMicroscopy, FluorescenceRNAgamma-H2AX protein, mouseHistonesHMGB1 ProteinHMGB2 ProteinRNATelomerasetelomerase RNATert protein, mouse

Identifiers

PMID22544226
OpenAlexW2034674750

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.