Vodenicharov M D, Sallmann F R, Satoh M S, Poirier G G
Poly(ADP-ribose) Metabolism Group and DNA Repair Group, Health and Environment Unit, Laval University Medical Research Center, CHUQ and Faculty of Medicine, Laval University, 2705 Boulevard Laurier, Ste-Foy, Quebec G1V 4G2, Canada.
Nucleic Acids Res. 2000 Oct 15;28(20):3887-96. doi: 10.1093/nar/28.20.3887.
Poly(ADP-ribose) polymerase 1 (PARP-1) is a nuclear enzyme that is activated by binding to DNA breaks induced by ionizing radiation or through repair of altered bases in DNA by base excision repair. Mice lacking PARP-1 and, in certain cases, the cells derived from these mice exhibit hypersensitivity to ionizing radiation and alkylating agents. In this study we investigated base excision repair in cells lacking PARP-1 in order to elucidate whether their augmented sensitivity to DNA damaging agents is due to an impairment of the base excision repair pathway. Extracts prepared from wild-type cells or cells lacking PARP-1 were similar in their ability to repair plasmid DNA damaged by either X-rays (single-strand DNA breaks) or by N:-methyl-N:'-nitro-N:-nitrosoguanidine (methylated bases). In addition, we demonstrated in vivo that PARP-1-deficient cells treated with N:-methyl-N:'-nitro-N:-nitrosoguanidine repaired their genomic DNA as efficiently as wild-type cells. Therefore, we conclude that cells lacking PARP-1 have a normal capacity to repair single-strand DNA breaks inflicted by X-irradiation or breaks formed during the repair of modified bases. We propose that the hypersensitivity of PARP-1 null mutant cells to gamma-irradiation and alkylating agents is not directly due to a defect in DNA repair itself, but rather results from greatly reduced poly(ADP-ribose) formation during base excision repair in these cells.
聚（ADP - 核糖）聚合酶1（PARP - 1）是一种核酶，它通过与电离辐射诱导的DNA断裂结合或通过碱基切除修复来修复DNA中改变的碱基而被激活。缺乏PARP - 1的小鼠以及在某些情况下源自这些小鼠的细胞对电离辐射和烷化剂表现出超敏反应。在本研究中，我们研究了缺乏PARP - 1的细胞中的碱基切除修复，以阐明它们对DNA损伤剂增强的敏感性是否由于碱基切除修复途径的损害。从野生型细胞或缺乏PARP - 1的细胞制备的提取物在修复受X射线（单链DNA断裂）或N - 甲基 - N' - 硝基 - N - 亚硝基胍（甲基化碱基）损伤的质粒DNA的能力方面相似。此外，我们在体内证明，用N - 甲基 - N' - 硝基 - N - 亚硝基胍处理的PARP - 1缺陷细胞修复其基因组DNA的效率与野生型细胞相同。因此，我们得出结论，缺乏PARP - 1的细胞具有修复X射线照射造成的单链DNA断裂或修饰碱基修复过程中形成的断裂的正常能力。我们提出，PARP - 1基因敲除突变细胞对γ射线和烷化剂的超敏性并非直接由于DNA修复本身的缺陷，而是由于这些细胞在碱基切除修复过程中聚（ADP - 核糖）形成大大减少所致。
