Abstract
Protein ADP-ribosylation is a reversible post-translational modification (PTM) process that plays fundamental roles in cell signaling. The covalent attachment of ADP ribose polymers is executed by PAR polymerases (PARP) and it is essential for chromatin organization, DNA repair, cell cycle, transcription, and replication, among other critical cellular events. The process of PARylation or polyADP-ribosylation is dynamic and takes place across many tissues undergoing renewal and repair, but the molecular mechanisms regulating this PTM remain mostly unknown. Here, we introduce the use of the planarian Schmidtea mediterranea as a tractable model to study PARylation in the complexity of the adult body that is under constant renewal and is capable of regenerating damaged tissues. We identified the evolutionary conservation of PARP signaling that is expressed in planarian stem cells and differentiated tissues. We also demonstrate that Smed-PARP-3 homolog is required for proper regeneration of tissues in the anterior region of the animal. Furthermore, our results demonstrate, Smed-PARP-3(RNAi) disrupts the timely location of injury-induced cell death near the anterior facing wounds and also affects the regeneration of the central nervous system. Our work reveals novel roles for PARylation in large-scale regeneration and provides a simplified platform to investigate PARP signaling in the complexity of the adult body.
Highlights
ADP-ribosylation (PARylation) is catalyzed by poly (ADP-ribose) polymerases (PARPs)
To identify whether PARP signaling is conserved in planarians, we used sequences corresponding to the 17 human PARP proteins and BLASTed them into the S. mediterranea genome (Figure 1A) [21]
We demonstrated that PARP signaling regulated large-scale tissue regeneration in planarians
Summary
ADP-ribosylation (PARylation) is catalyzed by poly (ADP-ribose) polymerases (PARPs). PARylation is an integral response that appears rapidly at sites of damaged DNA and establishes its effect through post-translational protein modifications [4,6,7]. PARPs are well characterized for their activation by single and double-stranded DNA breaks through the use of NAD+ substrates [2,3,5,8,9]. PARPs target proteins by the transfer of ADPR moieties through a 2’,1”-O-glycosidic ribose-ribose bond, producing a long and repetitive PAR chain containing an estimated 200 ADPR units in length [1,3,9]. The regulation and most of the PARP protein functions remain poorly understood
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