Lallev A, Anachkova B, Russev G
Institute of Molecular Biology, Bulgarian Academy of Sciences, Sofia.
Eur J Biochem. 1993 Aug 15;216(1):177-81. doi: 10.1111/j.1432-1033.1993.tb18130.x.
We have used a novel, quantitative approach to study the effect of gamma-radiation and topoisomerase-II inhibitors on the initiation of DNA synthesis in eukaryotic cells. We found out that mild gamma-irradiation caused an almost immediate decrease in the rate of initiation of genomic DNA replication and stimulated DNA repair. This held true for two different cell lines. Ehrlich ascites tumor cells and Friend transformed erythroid cells, although the effect of gamma-radiation on Friend cells was more pronounced. At the same time, the synthesis of mitochondrial DNA was not affected by the irradiation. The effect of topoisomerase-II inhibitors on DNA initiation closely paralleled that of gamma irradiation, but did not stimulate repair. The fact that gamma-radiation and topoisomerase-II inhibitors, two types of agents that differ so profoundly, have practically the same effect on DNA synthesis speaks strongly in favour of the idea that eukaryotic cells have a general mechanism for coping with any disturbances in DNA integrity and chromatin structure. This mechanism is probably similar to the SOS-mechanism of prokaryotic cells and includes, as an early step, a slowdown of the initiation of replicative DNA synthesis.
我们采用了一种全新的定量方法来研究γ辐射和拓扑异构酶II抑制剂对真核细胞中DNA合成起始的影响。我们发现，轻度γ辐射几乎会立即导致基因组DNA复制起始速率下降，并刺激DNA修复。两种不同的细胞系，即艾氏腹水瘤细胞和弗瑞德转化红细胞系，均是如此，尽管γ辐射对弗瑞德细胞的影响更为显著。与此同时，线粒体DNA的合成不受辐射影响。拓扑异构酶II抑制剂对DNA起始的影响与γ辐射极为相似，但不会刺激修复。γ辐射和拓扑异构酶II抑制剂这两种差异极大的试剂对DNA合成具有几乎相同的影响，这一事实有力地支持了真核细胞具有应对DNA完整性和染色质结构任何干扰的通用机制这一观点。该机制可能类似于原核细胞的SOS机制，并且作为早期步骤，包括复制性DNA合成起始的减缓。
