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Related Experiment Videos

Surviving apoptosis.

A T M Vaughan1, C J Betti, M J Villalobos

  • 1Department of Radiation Oncology, Loyola University Medical Center, 2160 South First Avenue, Building 112, Maywood, Illinois 60153, USA. avaugha@lumc.edu

Apoptosis : an International Journal on Programmed Cell Death
|February 28, 2002
PubMed
Summary
This summary is machine-generated.

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Cells surviving apoptosis can still undergo DNA damage, leading to leukemogenic translocations. This challenges the notion that chromatin cleavage during apoptosis always results in cell death.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Apoptosis involves chromatin cleavage by activated nucleases, like caspase-activated deoxyribonuclease (CAD).
  • Caspase activation and subsequent nuclease activity are not always lethal, as cells can survive transient apoptotic signaling.
  • Inhibitors of Apoptotic Programmed Cell Death Proteins (IAPs) can protect cells from nuclease-mediated damage.

Purpose of the Study:

  • To investigate the role of apoptosis-associated DNA damage in generating leukemogenic translocations.
  • To explore how cells surviving the apoptotic cascade can harbor DNA alterations.
  • To examine the MLL gene as a potential target for apoptosis-mediated translocations.

Main Methods:

  • Analysis of caspase activation and nuclease activity in cells undergoing transient apoptosis.

Related Experiment Videos

  • Investigation of Inhibitors of Apoptotic Programmed Cell Death Proteins (IAPs) in cell survival.
  • Identification of translocations within the MLL gene in relation to apoptotic nuclease attack.
  • Main Results:

    • Demonstration that cells can survive caspase activation and nuclease activity despite apoptotic morphology.
    • Identification of specific translocation breakpoints within the MLL gene at sites of apoptotic nuclease cleavage.
    • Evidence suggesting that MLL gene translocations can arise from DNA damage during a potentially survivable apoptotic event.

    Conclusions:

    • Chromatin cleavage during apoptosis does not invariably lead to cell death.
    • Transient caspase activation followed by recovery can result in DNA damage and oncogenic translocations.
    • Apoptosis-mediated DNA damage, particularly in genes like MLL, represents a novel mechanism contributing to leukemogenesis.