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Curr Opin Chem Biol. 2007 Dec;11(6):644-53. Epub 2007 Oct 23.

Poly(ADP-ribose) makes a date with death.

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Department of Chemistry, Roger Adams Laboratory, University of Illinois, Urbana, IL 61801, USA.


Poly(ADP-ribose) polymerase (PARP) enzymes catalyze the conversion of NAD(+) to polymers of poly(ADP-ribose) (PAR). Although its role in the DNA-damage response has long been recognized, recent work indicates that PAR itself acts at the mitochondria to directly induce cell death through stimulation of apoptosis-inducing factor (AIF) release. This review discusses PAR synthesis and degradation, and the role of PAR misregulation in various disease states. Attention is given to opportunities for therapeutic intervention with small molecules that are involved in PAR signaling, with specific focus on poly(ADP-ribose) glycohydrolase (PARG) and AIF.

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