Osheroff N, Zechiedrich E L, Gale K C
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146.
Bioessays. 1991 Jun;13(6):269-73. doi: 10.1002/bies.950130603.
Although the genetic code is defined by a linear array of nucleotides, it is the three-dimensional structure of the double helix that regulates most of its cellular functions. Over the past two decades, it has become increasingly clear that aspects of this three-dimensionality which reflect topological relationships within the double helix (i.e., superhelical twisting, knotting, or tangling) influence virtually every facet of nucleic acid physiology. In vivo, DNA topology is modulated by ubiquitous enzymes known as topoisomerases. The type II enzyme is essential to the eukaryotic cell and is required for unlinking daughter chromosomes and maintaining chromosome structure. Moreover, topoisomerase II also has been identified as the primary cellular target for several widely used antineoplastic drugs. Before the physiological functions of topoisomerase II can be effectively dissected or its drug interactions fully exploited, it is imperative to understand the mechanism by which this important enzyme carries out its catalytic cycle.
尽管遗传密码由核苷酸的线性阵列定义，但双螺旋的三维结构却调节着其大部分细胞功能。在过去二十年中，越来越清楚的是，这种反映双螺旋内拓扑关系（即超螺旋扭曲、打结或缠结）的三维特性几乎影响核酸生理学的方方面面。在体内，DNA拓扑结构由被称为拓扑异构酶的普遍存在的酶调节。II型酶对真核细胞至关重要，是解开子代染色体和维持染色体结构所必需的。此外，拓扑异构酶II也已被确定为几种广泛使用的抗肿瘤药物的主要细胞靶点。在能够有效剖析拓扑异构酶II的生理功能或充分利用其药物相互作用之前，必须了解这种重要酶进行催化循环的机制。
