Department of Pathology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
Department of Pathology, UT Southwestern Medical Center, Dallas, TX, 75390, USA; Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
DNA Repair (Amst). 2019 Sep;81:102651. doi: 10.1016/j.dnarep.2019.102651. Epub 2019 Jul 8.
Poly(ADP-ribose) (PAR) polymerase-1 (PARP-1) acts as a DNA damage sensor. It recognizes DNA damage and facilitates DNA repair by recruiting DNA repair machinery to damage sites. Recent studies reported that PARP-1 also plays an important role in DNA replication by recognizing the unligated Okazaki fragments and controlling the speed of fork elongation. On the other hand, emerging evidence reveals that excessive activation of PARP-1 causes chromatin DNA fragmentation and triggers an intrinsic PARP-1-dependent cell death program designated parthanatos, which can be blocked by genetic deletion or pharmacological inhibition of PARP-1. Therefore, PARP-1 plays an essential role in maintaining genomic stability by either facilitating DNA repair/replication or triggering DNA fragmentation to kill cells. A group of structure-specific nucleases is crucial for executing DNA incision and fragmentation following PARP-1 activation. In this review, we will discuss how PARP-1 coordinates with its associated nucleases to maintain genomic integrity and control the decision of cell life and death.
多聚（ADP-核糖）聚合酶 1（PARP-1）作为 DNA 损伤传感器。它通过招募 DNA 修复机制到损伤部位来识别 DNA 损伤并促进 DNA 修复。最近的研究报告称，PARP-1 通过识别未连接的冈崎片段并控制叉延伸速度，在 DNA 复制中也起着重要作用。另一方面，新出现的证据表明，PARP-1 的过度激活导致染色质 DNA 片段化，并触发一种内在的 PARP-1 依赖性细胞死亡程序，称为 parthanatos，可以通过 PARP-1 的遗传缺失或药理学抑制来阻断。因此，PARP-1 通过促进 DNA 修复/复制或触发 DNA 片段化来杀死细胞，从而在维持基因组稳定性方面发挥重要作用。一组结构特异性核酸内切酶对于 PARP-1 激活后执行 DNA 切割和片段化至关重要。在这篇综述中，我们将讨论 PARP-1 如何与相关的核酸内切酶协调，以维持基因组完整性并控制细胞生死的决定。
