Initiation of DNA fragmentation during apoptosis induces phosphorylation of H2AX histone at serine 139

Emmy P. Rogakou, Wilberto Nieves-Neira, Chye Boon, Yves Pommier, William M. Bonner

Research output: Contribution to journalArticle

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Abstract

Histone H2AX is a ubiquitous member of the H2A histone family that differs from the other H2A histones by the presence of an evolutionarily conserved C-terminal motif, -KKATQASQEY. The serine residue in this motif becomes rapidly phosphorylated in cells and animals when DNA double-stranded breaks are introduced into their chromatin by various physical and chemical means. In the present communication we show that this phosphorylated form of H2AX, referred to as γ-H2AX, appears during apoptosis concurrently with the initial appearance of high molecular weight DNA fragments. γ-H2AX forms before the appearance of internucleosomal DNA fragments and the externalization of phosphatidylserine to the outer membrane leaflet, γ-H2AX formation is inhibited by N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone and the inhibitor of caspase-activated DNase, and it is induced when DNase I and restriction enzymes are introduced into cells, suggesting that any apoptotic endonuclease is sufficient to induce γ-H2AX formation. These results indicate that γ-H2AX formation is an early chromatin modification following initiation of DNA fragmentation during apoptosis.

Original languageEnglish (US)
Pages (from-to)9390-9395
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number13
DOIs
StatePublished - Mar 31 2000

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Phosphorylation
DNA Fragmentation
Histones
Serine
Apoptosis
Chromatin
DNA
Double-Stranded DNA Breaks
Endonucleases
Deoxyribonuclease I
Phosphatidylserines
Ketones
Molecular Weight
Animals
Membranes
Molecular weight
Enzymes
Communication

ASJC Scopus subject areas

  • Biochemistry

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Initiation of DNA fragmentation during apoptosis induces phosphorylation of H2AX histone at serine 139. / Rogakou, Emmy P.; Nieves-Neira, Wilberto; Boon, Chye; Pommier, Yves; Bonner, William M.

In: Journal of Biological Chemistry, Vol. 275, No. 13, 31.03.2000, p. 9390-9395.

Research output: Contribution to journalArticle

Rogakou, Emmy P. ; Nieves-Neira, Wilberto ; Boon, Chye ; Pommier, Yves ; Bonner, William M. / Initiation of DNA fragmentation during apoptosis induces phosphorylation of H2AX histone at serine 139. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 13. pp. 9390-9395.
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