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The nuclear γ-H2AX apoptotic ring: implications for cancers and autoimmune diseases

Stéphanie Solier1, Yves Pommier

  • 1Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bldg. 37, Rm.5068, NIH, Bethesda, MD, 20892-4255, USA.

Cellular and Molecular Life Sciences : CMLS
|January 23, 2014
PubMed

Insights

Scientists discovered the apoptotic ring, an intranuclear shell of epigenetic modifications and DNA damage response proteins, appearing early in apoptosis. This finding offers potential as a biomarker for cancer therapies.

Area of Science:

  • Cell biology
  • Molecular biology
  • Cancer research

Background:

  • Apoptosis is crucial for development and implicated in immune diseases, cancers, and chemotherapy outcomes.
  • Apoptosis occurs via intrinsic (mitochondria-mediated) and extrinsic (death receptor-mediated) pathways.
  • Cancer therapies often target apoptosis to eliminate malignant cells.

Purpose of the Study:

  • To summarize current knowledge of the apoptotic ring.
  • To discuss its biological and pathophysiological significance.
  • To explore its utility as a pharmacodynamic biomarker for anticancer treatments.

Main Methods:

  • Microscopic observation of nuclear annular staining in early apoptosis.
  • 3D structural analysis of the intranuclear shell.
  • Characterization of epigenetic modifications and DNA damage response (DDR) proteins within the ring.

Main Results:

  • The apoptotic ring is a thick intranuclear shell observed early in apoptosis.
  • It comprises epigenetic modifications and DDR proteins, including histone H2AX.
  • The ring excludes typical DDR protein foci associated with γ-H2AX.

Conclusions:

  • The apoptotic ring represents a novel structural and molecular feature of early apoptosis.
  • It has significant biological and pathophysiological relevance.
  • The apoptotic ring shows promise as a pharmacodynamic biomarker for evaluating anticancer therapies.

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