Journal
CURRENT OPINION IN CHEMICAL BIOLOGY
Volume 11, Issue 6, Pages 644-653Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.cbpa.2007.08.038
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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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