Evidence map›Paper›PMID 14585993›Full record

ArticleMolecular and cellular biology2003

Human heterochromatin protein 1 isoforms HP1(Hsalpha) and HP1(Hsbeta) interfere with hTERT-telomere interactions and correlate with changes in cell growth and response to ionizing radiation.

Girdhar G Sharma, Kyu-kye Hwang, Raj K Pandita, Arun Gupta, Sonu Dhar, Julie Parenteau, Manjula Agarwal, Howard J Worman, Raymund J Wellinger, Tej K Pandita

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

50 citing papers in PubMed, 92 citations in OpenAlex.

  1. Article
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  10. Article
  11. Detecting ATM-dependent chromatin modification in DNA damage response.Methods in molecular biology (Clifton, N.J.) · 2015
    Article
  12. Article
  13. HP1 knockdown is associated with abnormal condensation of almost all chromatin types in a grasshopper (Eyprepocnemis plorans).Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2014
    Article
  14. Article
  15. Article
  16. Telomerase and its extracurricular activities.Cellular & molecular biology letters · 2013
    Review
  17. Article
  18. Article
  19. Article
  20. Targeting of Nrf2 induces DNA damage signaling and protects colonic epithelial cells from ionizing radiation.Proceedings of the National Academy of Sciences of the United States of America · 2012
    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

10 authors at 4 institutions in 2 countries.

Girdhar G SharmaRadiation and Cancer Biology Division, Washington University School of Medicine, 4511 Forest Park, St Louis, MO 63108, USA
Kyu-kye Hwang
Raj K Pandita
Arun Gupta
Sonu Dhar
Julie Parenteau
Manjula Agarwal
Howard J Worman
Raymund J Wellinger
Tej K Pandita
Washington University in St. Louis · USColumbia University · USUniversité de Sherbrooke · CAAlbert Einstein College of Medicine · US

Funding

CHROMATIN-TELOMERE STRUCTURE AND AT GENOMIC SENSITIVITYR01NS034746 · NINDS · WASHINGTON UNIVERSITY · PI PANDITA, TEJ K · 1996 to 2005
$1.2M
PATHOBIOLOGY OF THE NUCLEAR ENVELOPE IN CANCERR01CA066974 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI WORMAN, HOWARD J · 1996 to 2000
$287k
NCI NIH HHS R01 CA 66974NINDS NIH HHS NS 34746NINDS NIH HHS R01 NS034746
6 · The paper itself

Abstract

Telomeres are associated with the nuclear matrix and are thought to be heterochromatic. We show here that in human cells the overexpression of green fluorescent protein-tagged heterochromatin protein 1 (GFP-HP1) or nontagged HP1 isoforms HP1(Hsalpha) or HP1(Hsbeta), but not HP1(Hsgamma), results in decreased association of a catalytic unit of telomerase (hTERT) with telomeres. However, reduction of the G overhangs and overall telomere sizes was found in cells overexpressing any of these three proteins. Cells overexpressing HP1(Hsalpha) or HP1(Hsbeta) also display a higher frequency of chromosome end-to-end associations and spontaneous chromosomal damage than the parental cells. None of these effects were observed in cells expressing mutants of GFP-DeltaHP1(Hsalpha), GFP-DeltaHP1(Hsbeta), or GFP-DeltaHP1(Hsgamma) that had their chromodomains deleted. An increase in the cell population doubling time and higher sensitivity to cell killing by ionizing radiation (IR) treatment was also observed for cells overexpressing HP1(Hsalpha) or HP1(Hsbeta). In contrast, cells expressing mutant GFP-DeltaHP1(Hsalpha) or GFP-DeltaHP1(Hsbeta) showed a decrease in population doubling time and decreased sensitivity to IR compared to the parental cells. The effects on cell doubling times were paralleled by effects on tumorigenicity in mice: overexpression of HP1(Hsalpha) or HP1(Hsbeta) suppressed tumorigenicity, whereas expression of mutant HP1(Hsalpha) or HP1(Hsbeta) did not. Collectively, the results show that human cells are exquisitely sensitive to the amount of HP1(Hsalpha) or HP1(Hsbeta) present, as their overexpression influences telomere stability, population doubling time, radioresistance, and tumorigenicity in a mouse xenograft model. In addition, the isoform-specific effects on telomeres reinforce the notion that telomeres are in a heterochromatinized state.

Indexed as

AnimalsCarrier ProteinsCell DivisionCell LineCell SurvivalCell Transformation, NeoplasticChromobox Protein Homolog 5Chromosomal Proteins, Non-HistoneDNA-Binding ProteinsDNA RepairGreen Fluorescent ProteinsHeterochromatinHumansLuminescent ProteinsMiceProtein IsoformsCarrier ProteinsChromobox Protein Homolog 5Chromosomal Proteins, Non-HistoneDNA-Binding ProteinsGreen Fluorescent ProteinsHeterochromatinLuminescent ProteinsProtein IsoformsRecombinant Fusion ProteinsTelomerase

Identifiers

PMID14585993
PMCPMC262350
OpenAlexW2136271640

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.