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Published on: September 28, 2012

Involvement of histone H1.2 in apoptosis induced by DNA double-strand breaks

Akimitsu Konishi1, Shigeomi Shimizu, Junko Hirota

  • 1Department of Post-Genomics and Diseases, Osaka University Medical School, 2-2 Yamadaoka, Suita, 565-0871, Osaka, Japan.

Cell
|September 25, 2003
PubMed

Insights

Histone H1.2 transmits DNA damage signals to mitochondria, initiating apoptosis. This protein is crucial for transmitting apoptotic signals following DNA double-strand breaks, enhancing cellular resistance when its expression is reduced.

Area of Science:

  • Cellular biology
  • Molecular biology
  • Genetics

Background:

  • Apoptotic signals from DNA damage transmission to mitochondria remain unclear.
  • Mitochondria release factors activating downstream destruction programs.

Purpose of the Study:

  • Identify the factor transmitting apoptotic signals from nucleus to mitochondria after DNA damage.
  • Investigate the role of histone H1.2 in apoptosis.

Main Methods:

  • Identified histone H1.2 as a cytoplasmic factor post-X-ray irradiation.
  • Assessed H1.2's effect on cytochrome c release from isolated mitochondria.
  • Reduced H1.2 expression to evaluate cellular apoptosis resistance.
  • Examined apoptosis resistance in H1.2-deficient mice.

Main Results:

  • Histone H1.2, but not other H1 forms, induced cytochrome c release in a Bak-dependent manner.
  • Reduced H1.2 expression increased resistance to X-ray or etoposide-induced apoptosis.
  • H1.2 deficiency conferred resistance to X-ray-induced apoptosis in thymocytes and small intestine.

Conclusions:

  • Histone H1.2 is a key mediator in transmitting apoptotic signals from the nucleus to mitochondria after DNA double-strand breaks.
  • H1.2 plays a specific role in DNA damage-induced apoptosis pathways.

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