A Matter of Life and Cell Death

A cell has more than one option when it comes to protecting itself and surrounding tissues against the repercussions of DNA damage.

Written byStuart Blackman

| 6 min read

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Mild damage to DNA activates the DNA repair machinery. But severe insults will induce PARP-1 overactivation and cell death, which can occur independently of caspases. PARP-1 overactivation induces nuclear cell-death signaling (decreased NAD⁺and ATP) and causes apoptosis-inducing factor (AIF) to translocate from mitochondria to the nucleus. Reactive oxygen species and other damaging agents might activate the mitochondrial permeability transition (MPT) leading to the AIF release, and AIF and endonuclease G (EndoG) may act together. (adapted from S.J. Hong et al., Trends Pharmocol Sci, 25:259–64, 2004.)

A cell has more than one option when it comes to protecting itself and surrounding tissues against the repercussions of DNA damage. One approach is repair; another is to cut losses and sacrifice itself. Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear protein that appears to play a hand in both DNA repair and cell death.

"PARP is doing a very simple ...

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