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Histone released on cell death charges

DNA damage-induced apoptosis relies on histone H1.2 release into the cytosol

David Secko(dmsecko@interchange.ubc.ca)

Apoptosis is a highly regulated cell death mechanism employed by organisms to regulate tissue growth, control developmental processes, and eliminate harmful cells. Mitochondria play a central role in apoptosis by releasing molecules (such as cytochrome c) that activate the caspase pathways to lead to cell death. Many proteins have been linked to this mitochondrial release—including p53 and the Bcl-2 family of proteins (e.g., Bcl-2, Bcl-xL, Bax, Bak) that directly modulate outer mitochondrial membrane permeability—but how nuclear DNA damage is linked to the mitochondria during apoptosis has been unclear. In the September 19 Cell, Akimitsu Konishi and colleagues at the Osaka University Medical School report that DNA damage induces the release of histone H1.2, inducing cytochrome c release and leading to apoptosis (Cell, 114:673-688, September 19, 2003).

Konishi et al. used an in vitro assay that monitored the release of cytochrome c from isolated rat liver mitochondria. This assay allowed...

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