Department of Molecular and Cell Biology, University of California, Merced, CA 95340, USA.
Quantitative and Systems Biology Graduate Program, University of California, Merced, CA 95340, USA.
Int J Mol Sci. 2020 Jan 29;21(3):875. doi: 10.3390/ijms21030875.
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 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 homolog is required for proper regeneration of tissues in the anterior region of the animal. Furthermore, our results demonstrate, 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.
蛋白 ADP-核糖基化是一种可逆的翻译后修饰（PTM）过程，在细胞信号转导中发挥着基本作用。ADP 核糖聚合物的共价连接由 PAR 聚合酶（PARP）执行，对于染色质组织、DNA 修复、细胞周期、转录和复制等关键细胞事件至关重要。PARylation 或多 ADP-核糖基化的过程是动态的，发生在许多经历更新和修复的组织中，但调节这种 PTM 的分子机制在很大程度上仍然未知。在这里，我们介绍了使用扁形虫作为一个易于处理的模型来研究成年体内复杂的 PARylation，因为成年体内的组织处于不断更新和能够再生受损组织的状态。我们发现 PARP 信号在扁形虫干细胞和分化组织中表达具有进化上的保守性。我们还证明了 同源物对于动物前部组织的正常再生是必需的。此外，我们的结果表明， 缺失会破坏损伤诱导的细胞死亡在动物前向伤口附近的适时定位，也会影响中枢神经系统的再生。我们的工作揭示了 PARylation 在大规模再生中的新作用，并提供了一个简化的平台来研究成年体内复杂环境中的 PARP 信号。
