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J Biol Chem, Vol. 275, Issue 13, 9390-9395, March 31, 2000
From the Laboratory of Molecular Pharmacology, Division of Basic
Sciences, NCI, National Institutes of Health,
Bethesda, Maryland 20892
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
Initiation of DNA Fragmentation during Apoptosis Induces
Phosphorylation of H2AX Histone at Serine 139*
,
-H2AX, appears during apoptosis concurrently with the initial
appearance of high molecular weight DNA fragments. -H2AX forms
before the appearance of internucleosomal DNA fragments and the
externalization of phosphatidylserine to the outer membrane leaflet.
-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 -H2AX formation.
These results indicate that -H2AX formation is an early chromatin
modification following initiation of DNA fragmentation during apoptosis.
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: NCI, Bldg. 37, Rm.
5D21, National Institutes of Health, Bethesda, MD 20892. Tel.: 301-402-3649; Fax: 301-402-0752; E-mail: emrog@helix.nih.gov.
§
Present address: Division of Gynecologic Oncology, Jackson Memorial
Hospital, 1611 N. N. 12th Ave., Miami, FL 33136.
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