Initiation of DNA Fragmentation during Apoptosis Induces Phosphorylation of H2AX Histone at Serine 139*

By E. Rogakou, W. Nieves‐Neira, C. Boon, Yves Pommier, W. Bonner. Journal of Biological Chemistry, 2000

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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 byN-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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/ff3ceaf8c373f0b8b2a7944c799a784a1df05aa5

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Citations in the corpus

The γ‐H2A.X: Is it just a surrogate marker of double‐strand breaks or much more? (2008, background): “X phosphorylation appears at sites of DSBs during DSB repair, meiotic recombination [Hunter et al., 2001; Mahadevaiah et al., 2001], apoptotic digestion [Rogakou et al., 2000], V (D) J splicing [Chen et al., 2000; Gellert, 2002], and class switch recombination [Petersen et al., 2001].”
The JNK signal transduction pathway. (2007, positive): “Previous studies have suggested that H2AX phosphorylation by members of the PIKK group of kinases is a consequence of apoptosis [41,42]; however, the recent study by Lu and colleagues indicates that JNK-mediated H2AX phosphorylation may be essential for DNA fragmentation in UV-stimulated cells [39].”
DNA damage-induced apoptosis (2004, background): “Furthermore, the kinetics of H2AX phosphorylation suggest that this chromatin Oncogene modification could be induced by apoptotic DNA fragmentation itself (Rogakou et al., 2000).”