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The apoptotic ring: A novel entity with phosphorylated histones H2AX and H2B, and activated DNA damage response kinases

Stéphanie Solier and Yves Pommier

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We recently showed that histone H2AX phosphorylated on serine 139 (γ-H2AX), a hallmark of DNA damage response (DDR), also forms early during apoptosis induced by death receptor activation. Here, we extend and discuss our findings on apoptotic γ-H2AX, which differs from the well-established DDR with nuclear foci. During apoptosis induced by death receptors agonists (TRAIL and FasL) and staurosporine, γ-H2AX is initiated in the nuclear periphery immediately inside the nuclear envelope while total H2AX remains distributed throughout the nucleus. This process is readily detectable by immunofluorescence microscopy and we refer to it as the “γ-H2AX ring”. It is conserved both in cancer and normal cells. The γ-H2AX ring contains the activated checkpoints kinases, ATM, Chk2 and DNA-PK; the latter being the main effector for the apoptotic γ-H2AX phosphorylation. Notably, we show here that the γ-H2AX ring coincides with phosphorylated H2B on serine 14 (PS14-H2B), another histone modification associated with apoptosis. The coordinated phosphorylations of H2AX and H2B suggest a previously unrecognized histone phosphorylation signature for apoptosis consisting of γ-H2AX together with PS14-H2B and possibly PY142-H2AX. This signature (“phospho-histone 2 code”) together with the γ-H2AX ring provides a new feature to monitor and study apoptosis.

Authors

Stéphanie Solier

National Cancer Institute; Bethesda, MD

Yves Pommier Corresponding author: pommier@nih.gov

National Cancer Institute; Bethesda, MD

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.