Evidence map›Paper›PMID 22253444›Full record

ArticleThe Journal of biological chemistry2012

Apoptotic DNA degradation into oligonucleosomal fragments, but not apoptotic nuclear morphology, relies on a cytosolic pool of DFF40/CAD endonuclease.

Victoria Iglesias-Guimarais, Estel Gil-Guiñon, Gisela Gabernet, Mercè García-Belinchón, María Sánchez-Osuna, Elisenda Casanelles, Joan X Comella, Victor J Yuste

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

11 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. The role of the DFF40/CAD endonuclease in genomic stability.Apoptosis : an international journal on programmed cell death · 2021
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. 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 3 institutions in 1 country.

Victoria Iglesias-GuimaraisCell Death, Senescence, and Survival Group, Departament de Bioquimica i Biologia Molecular and Institut de Neurociencies, Facultat de Medicina, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
Estel Gil-Guiñon
Gisela Gabernet
Mercè García-Belinchón
María Sánchez-Osuna
Elisenda Casanelles
Joan X Comella
Victor J Yuste
Universitat Autònoma de Barcelona · ESBiomedical Research Networking Center on Neurodegenerative Diseases · ESVall d'Hebron Institut de Recerca · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Apoptotic cell death is characterized by nuclear fragmentation and oligonucleosomal DNA degradation, mediated by the caspase-dependent specific activation of DFF40/CAD endonuclease. Here, we describe how, upon apoptotic stimuli, SK-N-AS human neuroblastoma-derived cells show apoptotic nuclear morphology without displaying concomitant internucleosomal DNA fragmentation. Cytotoxicity afforded after staurosporine treatment is comparable with that obtained in SH-SY5Y cells, which exhibit a complete apoptotic phenotype. SK-N-AS cell death is a caspase-dependent process that can be impaired by the pan-caspase inhibitor q-VD-OPh. The endogenous inhibitor of DFF40/CAD, ICAD, is correctly processed, and dff40/cad cDNA sequence does not reveal mutations altering its amino acid composition. Biochemical approaches show that both SH-SY5Y and SK-N-AS resting cells express comparable levels of DFF40/CAD. However, the endonuclease is poorly expressed in the cytosolic fraction of healthy SK-N-AS cells. Despite this differential subcellular distribution of DFF40/CAD, we find no differences in the subcellular localization of both pro-caspase-3 and ICAD between the analyzed cell lines. After staurosporine treatment, the preferential processing of ICAD in the cytosolic fraction allows the translocation of DFF40/CAD from this fraction to a chromatin-enriched one. Therefore, the low levels of cytosolic DFF40/CAD detected in SK-N-AS cells determine the absence of DNA laddering after staurosporine treatment. In these cells DFF40/CAD cytosolic levels can be restored by the overexpression of their own endonuclease, which is sufficient to make them proficient at degrading their chromatin into oligonucleosome-size fragments after staurosporine treatment. Altogether, the cytosolic levels of DFF40/CAD are determinants in achieving a complete apoptotic phenotype, including oligonucleosomal DNA degradation.

Indexed as

DNA FragmentationApoptosisApoptosis Regulatory ProteinsCaspase 3Cell Line, TumorDeoxyribonucleasesEnzyme InhibitorsHumansMutationPoly-ADP-Ribose Binding ProteinsStaurosporineApoptosis Regulatory ProteinsCaspase 3caspase-activated DNase inhibitorDeoxyribonucleasesDFFB protein, humanEnzyme InhibitorsPoly-ADP-Ribose Binding ProteinsStaurosporine

Identifiers

PMID22253444
PMCPMC3293563
OpenAlexW2042177864

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.