Poly(ADP-ribose) (PAR) is a nucleic acid-like protein modification that can seed the formation of microscopically visible cellular compartments that lack enveloping membranes, recently termed biomolecular condensates. These PAR-mediated condensates are linked to cancer, viral infection, and neurodegeneration. Recent data have shown the therapeutic potential of modulating PAR conjugation (PARylation): PAR polymerase (PARP) inhibitors can modulate the formation and dynamics of these condensates as well as the trafficking of their components - many of which are key disease factors. However, the way in which PARylation facilitates these functions remains unclear, partly because of our lack of understanding of the fundamental parameters of intracellular PARylation, including the sites that are conjugated, PAR chain length and structure, and the physicochemical properties of the conjugates. This review first introduces the role of PARylation in regulating biomolecular condensates, followed by discussion of current knowledge gaps, potential solutions, and therapeutic applications.

中文翻译：

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聚（ADP-核糖）：生物分子冷凝物形成的动态触发。

聚（ADP-核糖）（PAR）是一种核酸样蛋白质修饰，可播种形成缺乏包膜的显微镜下可见的细胞隔室，这种膜最近被称为生物分子缩合物。这些PAR介导的冷凝物与癌症，病毒感染和神经变性有关。最近的数据表明调节PAR共轭（PARylation）的治疗潜力：PAR聚合酶（PARP）抑制剂可调节这些凝析液的形成和动力学以及其组分的运输-其中许多是关键疾病因素。但是，PARylation促进这些功能的方式仍不清楚，部分原因是由于我们对细胞内PARylation的基本参数（包括结合位点，PAR链长和结构）缺乏了解，和结合物的理化性质。这篇综述首先介绍了PARylation在调节生物分子冷凝物中的作用，然后讨论了当前的知识差距，潜在的解决方案和治疗应用。