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The Sound of Silence: RNAi in Poly (ADP-Ribose) Research
Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, Winterthurerstrasse 260, 8057 Zurich, Switzerland
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 4 September 2012; in revised form: 5 November 2012 / Accepted: 6 November 2012 / Published: 6 December 2012
Abstract: Poly(ADP-ribosyl)-ation is a nonprotein posttranslational modification of proteins and plays an integral part in cell physiology and pathology. The metabolism of poly(ADP-ribose) (PAR) is regulated by its synthesis by poly(ADP-ribose) polymerases (PARPs) and on the catabolic side by poly(ADP-ribose) glycohydrolase (PARG). PARPs convert NAD+ molecules into PAR chains that interact covalently or noncovalently with target proteins and thereby modify their structure and functions. PAR synthesis is activated when PARP1 and PARP2 bind to DNA breaks and these two enzymes account for almost all PAR formation after genotoxic stress. PARG cleaves PAR molecules into free PAR and finally ADP-ribose (ADPR) moieties, both acting as messengers in cellular stress signaling. In this review, we discuss the potential of RNAi to manipulate the levels of PARPs and PARG, and consequently those of PAR and ADPR, and compare the results with those obtained after genetic or chemical disruption.
Keywords: ADPR; PAR; PARP1; PARP2; PARG; siRNA
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Blenn, C.; Wyrsch, P.; Althaus, F.R. The Sound of Silence: RNAi in Poly (ADP-Ribose) Research. Genes 2012, 3, 779-805.
Blenn C, Wyrsch P, Althaus FR. The Sound of Silence: RNAi in Poly (ADP-Ribose) Research. Genes. 2012; 3(4):779-805.
Blenn, Christian; Wyrsch, Philippe; Althaus, Felix R. 2012. "The Sound of Silence: RNAi in Poly (ADP-Ribose) Research." Genes 3, no. 4: 779-805.