Tzung T Y, Rünger T M
Department of Dermatology, Georg-August University, Göttingen, Germany.
Int J Radiat Biol. 1998 May;73(5):469-74. doi: 10.1080/095530098142004.
To characterize further the contribution of the DNA-PK-dependent dsb repair pathway in mammalian cells.
The efficiency and fidelity of the joining of linear plasmids by DNA-PKcs-defective mouse cells (SCID) and Ku80-defective Chinese hamster ovary cells (xrs-6) was measured using either linear or circular replicating shuttle vector pZ189.
The authors found a 3.9-10.7-fold reduced joining of the DNA ends, as compared with wild-type cells. Mutation analysis of the joining site revealed that the joining process was not hypermutable in the mutated cells. However, the SCID and xrs-6 cells produced a different spectrum of mutations at the joining site with a significantly lower proportion of insertions or more complex mutations.
The remaining joining ability of the mutant cells points to an alternative DNA-PK-independent pathway of dsb repair. Comparison of these data with similar data from yeast suggest that the postulated alternative pathway of dsb repair is at least as efficient and less error-prone in rodent cells.
进一步明确DNA依赖蛋白激酶（DNA-PK）相关的双链断裂（dsb）修复途径在哺乳动物细胞中的作用。
使用线性或环状复制穿梭载体pZ189，测定DNA-PKcs缺陷型小鼠细胞（SCID）和Ku80缺陷型中国仓鼠卵巢细胞（xrs-6）连接线性质粒的效率和保真度。
作者发现，与野生型细胞相比，DNA末端连接减少了3.9至10.7倍。连接位点的突变分析表明，在突变细胞中连接过程并非高度易变。然而，SCID和xrs-6细胞在连接位点产生了不同的突变谱，插入或更复杂突变的比例显著降低。
突变细胞剩余的连接能力表明存在一种不依赖DNA-PK的dsb修复替代途径。将这些数据与来自酵母的类似数据进行比较表明，假定的dsb修复替代途径在啮齿动物细胞中至少同样有效且错误倾向更低。
