Dantzer F, Schreiber V, Niedergang C, Trucco C, Flatter E, De La Rubia G, Oliver J, Rolli V, Ménissier-de Murcia J, de Murcia G
UPR 9003-CNRS, Laboratoire conventionné avec le Commissariat à l'Energie Atomique, Ecole Supérieure de Biotechnologie de Strasbourg, Illkirch-Graffenstaden, France.
Biochimie. 1999 Jan-Feb;81(1-2):69-75. doi: 10.1016/s0300-9084(99)80040-6.
Poly(ADP-ribose) polymerase (PARP) is a zinc-finger DNA binding protein that detects and signals DNA strand breaks generated directly or indirectly by genotoxic agents. In response to these lesions, the immediate poly(ADP-ribosylation) of nuclear proteins converts DNA interruptions into intracellular signals that activate DNA repair or cell death programs. To elucidate the biological function of PARP in vivo, the mouse PARP gene was inactivated by homologous recombination to generate mice lacking a functional PARP gene. PARP knockout mice and the derived mouse embryonic fibroblasts (MEFs) were acutely sensitive to monofunctional alkylating agents and gamma-irradiation demonstrating that PARP is involved in recovery from DNA damage that triggers the base excision repair (BER) process. To address the issue of the role of PARP in BER, the ability of PARP-deficient mammalian cell extracts to repair a single abasic site present on a circular duplex plasmid molecule was tested in a standard in vitro repair assay. The results clearly demonstrate, for the first time, the involvement of PARP in the DNA synthesis step of the base excision repair process.
聚（ADP - 核糖）聚合酶（PARP）是一种锌指DNA结合蛋白，可检测由基因毒性剂直接或间接产生的DNA链断裂并发出信号。针对这些损伤，核蛋白的即时聚（ADP - 核糖基化）将DNA中断转化为激活DNA修复或细胞死亡程序的细胞内信号。为了阐明PARP在体内的生物学功能，通过同源重组使小鼠PARP基因失活，以产生缺乏功能性PARP基因的小鼠。PARP基因敲除小鼠及其衍生的小鼠胚胎成纤维细胞（MEF）对单功能烷基化剂和γ射线高度敏感，表明PARP参与了触发碱基切除修复（BER）过程的DNA损伤修复。为了解决PARP在BER中的作用问题，在标准的体外修复试验中测试了PARP缺陷的哺乳动物细胞提取物修复环状双链质粒分子上单个无碱基位点的能力。结果首次清楚地证明了PARP参与碱基切除修复过程的DNA合成步骤。
