Effect of DNA polymerase inhibitors on DNA repair in intact and permeable human fibroblasts: evidence that DNA polymerases delta and beta are involved in DNA repair synthesis induced by N-methyl-N'-nitro-N-nitrosoguanidine.
Effect of DNA polymerase inhibitors on DNA repair in intact and permeable human fibroblasts: evidence that DNA polymerases delta and beta are involved in DNA repair synthesis induced by N-methyl-N'-nitro-N-nitrosoguanidine.
复制标题
DNA聚合酶抑制剂对完整且可渗透的人成纤维细胞DNA修复的影响：证据表明DNA聚合酶δ和β参与N-甲基-N-硝基-N-亚硝基胍诱导的DNA修复合成。
DOI：
10.1021/bi00453a039
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发表时间：
1990
期刊：
影响因子：
2.9
通讯作者：
Miller,MR
中科院分区：
文献类型：
--
作者：
Hammond,RA;McClung,JK;Miller,MR
（BuPdGTP）、双脱氧胸苷三磷酸（ddTTP）和阿非迪霉素对MNNG诱导的DNA修复合成的影响，以剖析不同DNA聚合酶的作用。一个亚细胞系统（渗透性细胞），其中DNA修复合成和DNA复制的区分由CsCl梯度离心BrdUMP密度标记的DNA，被用来检查聚合酶抑制剂的影响。另一种方法研究了这些抑制剂对MNNG诱导的完整细胞DNA修复合成的影响，方法是通过放射自显影和自动视频图像分析系统定量测定掺入修复DNA中的[3 H]胸苷的量。在渗透性细胞中，MNNG诱导的DNA修复合成被50 pg/mL的阿非迪霉素抑制56%，被10 µ BuPdGTP抑制6%，被抗（DNA聚合酶a）单克隆抗体抑制13%，被ddTTP抑制29%。在完整细胞中，MNNG诱导的DNA修复合成被50 pg/mL的aphidicolin抑制57%，并且通过将抗（DNA聚合酶a）抗体显微注射到HF细胞核中没有显著抑制。这些结果表明，DNA聚合酶和DNA聚合酶都参与了由DNA聚合酶引起的DNA损伤的修复。
(BuPdGTP), dideoxythymidine triphosphate (ddTTP), and aphidicolin on MNNG-induced DNA repair synthesis were investigated to dissect the roles of the different DNA polymerases. A subcellular system (permeable cells), in which DNA repair synthesis and DNA replication were differentiated by CsCl gradient centrifugation of BrdUMP density-labeled DNA, was used to examine the effects of the polymerase inhibitors. Another approach investigatedthe effects of several of these inhibitors on MNNG-induced DNA repair synthesis in intact cells by measuring the amount of [3H] thymidine incorporated into repaired DNA as determined by autoradiography and quantitation with an automated video image analysis system. In permeable cells, MNNG-induced DNA repair synthesis was inhibited 56% by 50 pg of aphidicolin/mL, 6% by 10 µ BuPdGTP, 13% by anti-(DNA polymerase a) monoclonal antibodies, and 29% by ddTTP. In intact cells, MNNG-induced DNA repair synthesis was inhibited 57% by 50 pg of aphidicolin/mL and was not significantly inhibited by microinjecting anti-(DNA polymerase a) antibodies into HF nuclei. These results indicatethat both DNA polymerases and ß are involved in repairing DNA damage caused by