Shall S, de Murcia G
UPR 9003 du Centre National de la Recherche Scientifique, Laboratoire conventionné avec le Commissariat à l'Energie Atomique, Ecole Supérieure de Biotechnologie de Strasbourg, France.
Mutat Res. 2000 Jun 30;460(1):1-15. doi: 10.1016/s0921-8777(00)00016-1.
Poly (ADP-ribose) polymerase (113 kDa; PARP-1) is a constitutive factor of the DNA damage surveillance network developed by the eukaryotic cell to cope with the numerous environmental and endogenous genotoxic agents. This enzyme recognizes and is activated by DNA strand breaks. This original property plays an essential role in the protection and processing of the DNA ends as they arise in DNA damage that triggers the base excision repair (BER) pathway. The generation, by homologous recombination, of three independent deficient mouse models have confirmed the caretaker function of PARP-1 in mammalian cells under genotoxic stress. Unexpectedly, the knockout strategy has revealed the instrumental role of PARP-1 in cell death after ischemia-reperfusion injury and in various inflammation process. Moreover, the residual PARP activity found in PARP-1 deficient cells has been recently attributed to a novel DNA damage-dependent poly ADP-ribose polymerase (62 kDa; PARP-2), another member of the expanding PARP family that, on the whole, appears to be involved in the genome protection. The present review summarizes the recent data obtained with the three PARP knockout mice in comparison with the chemical inhibitor approach.
聚（ADP - 核糖）聚合酶（113 kDa；PARP - 1）是真核细胞为应对众多环境和内源性基因毒性剂而建立的DNA损伤监测网络的一个组成因子。这种酶可识别DNA链断裂并被其激活。这一独特特性在DNA损伤引发碱基切除修复（BER）途径时对DNA末端的保护和处理过程中起着至关重要的作用。通过同源重组产生的三种独立的缺陷小鼠模型证实了PARP - 1在基因毒性应激下对哺乳动物细胞的维护功能。出乎意料的是，基因敲除策略揭示了PARP - 1在缺血再灌注损伤后的细胞死亡以及各种炎症过程中的重要作用。此外，最近在PARP - 1缺陷细胞中发现的残余PARP活性归因于一种新型的DNA损伤依赖性聚ADP - 核糖聚合酶（62 kDa；PARP - 2），它是不断扩大的PARP家族的另一个成员，总体上似乎参与了基因组保护。本综述总结了与化学抑制剂方法相比，利用三种PARP基因敲除小鼠获得的最新数据。
