PARP1 and PARP2 govern the DNA-damage response by catalysing the reversible post-translational modification ADP-ribosylation. During the repair of DNA lesions, PARP1 and PARP2 combine with an accessory factor HPF1, which is required for the modification of target proteins on serine residues. Although the physiological role of individual ADP-ribosylation sites is still unclear, serine ADP-ribosylation at damage sites leads to the recruitment of chromatin remodellers and repair factors to ensure efficient DNA repair. ADP-ribosylation signalling is tightly controlled by the coordinated activities of (ADP-ribosyl)glycohydrolases PARG and ARH3 that, by reversing the modification, guarantee proper kinetics of DNA repair and cell cycle re-entry. The recent advances in the structural and mechanistic understanding of ADP-ribosylation provide new insights into human physiopathology and cancer therapy.

PARP1 和 PARP2 通过催化可逆的翻译后修饰 ADP 核糖基化来控制 DNA 损伤反应。在 DNA 损伤修复过程中，PARP1 和 PARP2 与辅助因子 HPF1 结合，这是修饰丝氨酸残基上靶蛋白所必需的。尽管单个 ADP-核糖基化位点的生理作用仍不清楚，但损伤位点的丝氨酸 ADP-核糖基化会导致染色质重塑因子和修复因子的募集，以确保有效的 DNA 修复。ADP-核糖基化信号由 (ADP-核糖基) 糖水解酶 PARG 和 ARH3 的协调活动严格控制，通过逆转修饰，保证 DNA 修复和细胞周期重新进入的适当动力学。