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

Akimitsu Konishi, Shigeomi Shimizu, Junko Hirota, Toshifumi Takao, Yuhong Fan, Yosuke Matsuoka, Lilin Zhang, Yoshihiro Yoneda, Yoshitaka Fujii, Arthur I. Skoultchi, Yoshihide Tsujimoto

Research output: Contribution to journalArticle

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Abstract

It is poorly understood how apoptotic signals arising from DNA damage are transmitted to mitochondria, which release apoptogenic factors into the cytoplasm that activate downstream destruction programs. Here, we identify histone H1.2 as a cytochrome c-releasing factor that appears in the cytoplasm after exposure to X-ray irradiation. While all nuclear histone H1 forms are released into the cytoplasm in a p53-dependent manner after irradiation, only H1.2, but not other H1 forms, induced cytochrome c release from isolated mitochondria in a Bak-dependent manner. Reducing H1.2 expression enhanced cellular resistance to apoptosis induced by X-ray irradiation or etoposide, but not that induced by other stimuli including TNF-α and UV irradiation. H1.2-deficient mice exhibited increased cellular resistance in thymocytes and the small intestine to X-ray-induced apoptosis. These results indicate that histone H1.2 plays an important role in transmitting apoptotic signals from the nucleus to the mitochondria following DNA double-strand breaks.

Original languageEnglish (US)
Pages (from-to)673-688
Number of pages16
JournalCell
Volume114
Issue number6
DOIs
StatePublished - Sep 19 2003

Fingerprint

Double-Stranded DNA Breaks
Histones
Mitochondria
Cytoplasm
X-Rays
Irradiation
Apoptosis
Cytochromes c
DNA
X rays
Etoposide
Thymocytes
DNA Damage
Small Intestine

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Konishi, A., Shimizu, S., Hirota, J., Takao, T., Fan, Y., Matsuoka, Y., ... Tsujimoto, Y. (2003). Involvement of histone H1.2 in apoptosis induced by DNA double-strand breaks. Cell, 114(6), 673-688. https://doi.org/10.1016/S0092-8674(03)00719-0

Involvement of histone H1.2 in apoptosis induced by DNA double-strand breaks. / Konishi, Akimitsu; Shimizu, Shigeomi; Hirota, Junko; Takao, Toshifumi; Fan, Yuhong; Matsuoka, Yosuke; Zhang, Lilin; Yoneda, Yoshihiro; Fujii, Yoshitaka; Skoultchi, Arthur I.; Tsujimoto, Yoshihide.

In: Cell, Vol. 114, No. 6, 19.09.2003, p. 673-688.

Research output: Contribution to journalArticle

Konishi, A, Shimizu, S, Hirota, J, Takao, T, Fan, Y, Matsuoka, Y, Zhang, L, Yoneda, Y, Fujii, Y, Skoultchi, AI & Tsujimoto, Y 2003, 'Involvement of histone H1.2 in apoptosis induced by DNA double-strand breaks', Cell, vol. 114, no. 6, pp. 673-688. https://doi.org/10.1016/S0092-8674(03)00719-0
Konishi A, Shimizu S, Hirota J, Takao T, Fan Y, Matsuoka Y et al. Involvement of histone H1.2 in apoptosis induced by DNA double-strand breaks. Cell. 2003 Sep 19;114(6):673-688. https://doi.org/10.1016/S0092-8674(03)00719-0
Konishi, Akimitsu ; Shimizu, Shigeomi ; Hirota, Junko ; Takao, Toshifumi ; Fan, Yuhong ; Matsuoka, Yosuke ; Zhang, Lilin ; Yoneda, Yoshihiro ; Fujii, Yoshitaka ; Skoultchi, Arthur I. ; Tsujimoto, Yoshihide. / Involvement of histone H1.2 in apoptosis induced by DNA double-strand breaks. In: Cell. 2003 ; Vol. 114, No. 6. pp. 673-688.
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