Poly-ADP-ribose-polymerases (PARPs) are a family of 17 enzymes that regulate a diverse range of cellular processes in mammalian cells. PARPs catalyze the transfer of ADP-ribose from NAD⁺ to target molecules, most prominently amino acids on protein substrates, in a process known as ADP-ribosylation. Identifying the direct protein substrates of individual PARP family members is an essential first step for elucidating the mechanism by which PARPs regulate a particular pathway in cells. Two distinct chemical genetic (CG) strategies have been developed for identifying the direct protein substrates of individual PARP family members. In this review, we discuss the design principles behind these two strategies and how target identification has provided novel insight into the cellular function of individual PARPs and PARP-mediated ADP-ribosylation.

聚-ADP-核糖聚合酶 (PARP) 是一个由 17 种酶组成的家族，可调节哺乳动物细胞中的多种细胞过程。PARPs 催化 ADP-核糖从 NAD ^+转移在称为 ADP 核糖基化的过程中靶向分子，最突出的是蛋白质底物上的氨基酸。鉴定单个 PARP 家族成员的直接蛋白质底物是阐明 PARP 调节细胞中特定途径的机制的重要的第一步。已经开发了两种不同的化学遗传 (CG) 策略来识别单个 PARP 家族成员的直接蛋白质底物。在这篇综述中，我们讨论了这两种策略背后的设计原则，以及目标识别如何为单个 PARP 的细胞功能和 PARP 介导的 ADP 核糖基化提供新的见解。