Bakshi R P, Galande S, Muniyappa K
Department of Biochemistry, Indian Institute of Science, Bangalore.
Crit Rev Biochem Mol Biol. 2001;36(1):1-37. doi: 10.1080/20014091074165.
DNA topoisomerases are ubiquitous nuclear enzymes that govern the topological interconversions of DNA by transiently breaking/rejoining the phosphodiester backbone of one (type I) or both (type II) strands of the double helix. Consistent with these functions, topoisomerases play key roles in many aspects of DNA metabolism. Type II DNA topoisomerase (topo II) is vital for various nuclear processes, including DNA replication, chromosome segregation, and maintenance of chromosome structure. Topo II expression is regulated at multiple stages, including transcriptional, posttranscriptional, and posttranslational levels, by a multitude of signaling factors. Topo II is also the cellular target for a variety of clinically relevant anti-tumor drugs. Despite significant progress in our understanding of the role of topo II in diverse nuclear processes, several important aspects of topo II function, expression, and regulation are poorly understood. We have focused this review specifically on eukaryotic DNA topoisomerase II, with an emphasis on functional and regulatory characteristics.
DNA拓扑异构酶是普遍存在于细胞核中的酶,通过瞬时断裂/重新连接双螺旋中一条链(I型)或两条链(II型)的磷酸二酯主链来控制DNA的拓扑异构化。与这些功能一致,拓扑异构酶在DNA代谢的许多方面发挥着关键作用。II型DNA拓扑异构酶(拓扑异构酶II)对各种核过程至关重要,包括DNA复制、染色体分离和染色体结构的维持。拓扑异构酶II的表达在多个阶段受到多种信号因子的调控,包括转录、转录后和翻译后水平。拓扑异构酶II也是多种临床相关抗肿瘤药物的细胞靶点。尽管我们对拓扑异构酶II在各种核过程中的作用有了显著进展,但拓扑异构酶II功能、表达和调控的几个重要方面仍知之甚少。我们在这篇综述中特别关注真核生物DNA拓扑异构酶II,重点是其功能和调控特性。