Rzeszowska-Wolny J, Widłak P
Department of Experimental and Clinical Radiobiology, Institute of Oncology, Gliwice, Poland.
Acta Biochim Pol. 1999;46(1):173-80.
Proteins which bind to the DNA damaged by genotoxic agents can be detected in all living organisms. Damage-recognition proteins are thought to be generally involved in DNA repair mechanisms. On the other hand, the relevance to DNA repair of some other proteins which show elevated affinity to damaged DNA (e.g. HMG-box containing proteins or histone H1) has not been established. Using the electrophoretic mobility-shift assay we have investigated damage-recognition proteins in nuclei from rat hepatocytes. We detected two different protein complexes which preferentially bound the DNA damaged by N-acetoxy-acetylaminofluorene. One of them also recognized the DNA damaged by benzo(a)pyrene diol epoxide (yet with much lower efficiency). The proteins which bind to damaged DNA are permanently present in rat cells and their level does not change after treatment of animals with the carcinogens. Differences in the affinity of the detected damage-recognition proteins to DNA lesion evoked by either carcinogen did not correlate with more efficient removal from hepatic DNA of 2-acetylaminofluorene-induced adducts than benzo(a)pyrene-induced ones.
在所有生物体中都能检测到与基因毒性剂损伤的DNA结合的蛋白质。损伤识别蛋白通常被认为参与DNA修复机制。另一方面,一些对受损DNA表现出更高亲和力的其他蛋白质(例如含HMG盒的蛋白质或组蛋白H1)与DNA修复的相关性尚未确定。我们使用电泳迁移率变动分析研究了大鼠肝细胞细胞核中的损伤识别蛋白。我们检测到两种不同的蛋白质复合物,它们优先结合被N-乙酰氧基-乙酰氨基芴损伤的DNA。其中一种还能识别被苯并(a)芘二醇环氧化物损伤的DNA(但效率低得多)。与受损DNA结合的蛋白质在大鼠细胞中永久存在,在用致癌物处理动物后其水平不变。所检测到的损伤识别蛋白对两种致癌物诱发的DNA损伤的亲和力差异,与从肝DNA中更有效地去除2-乙酰氨基芴诱导的加合物而非苯并芘诱导的加合物无关。