Nitiss John L
Molecular Pharmacology Department, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Nat Rev Cancer. 2009 May;9(5):327-37. doi: 10.1038/nrc2608. Epub 2009 Apr 20.
DNA topoisomerases are enzymes that disentangle the topological problems that arise in double-stranded DNA. Many of these can be solved by the generation of either single or double strand breaks. However, where there is a clear requirement to alter DNA topology by introducing transient double strand breaks, only DNA topoisomerase II (TOP2) can carry out this reaction. Extensive biochemical and structural studies have provided detailed models of how TOP2 alters DNA structure, and recent molecular studies have greatly expanded knowledge of the biological contexts in which TOP2 functions, such as DNA replication, transcription and chromosome segregation -- processes that are essential for preventing tumorigenesis.
DNA拓扑异构酶是一类能够解决双链DNA中出现的拓扑学问题的酶。其中许多问题可以通过产生单链或双链断裂来解决。然而,在明确需要通过引入瞬时双链断裂来改变DNA拓扑结构的情况下,只有DNA拓扑异构酶II(TOP2)能够进行这一反应。广泛的生化和结构研究提供了TOP2改变DNA结构的详细模型,最近的分子研究极大地扩展了我们对TOP2发挥功能的生物学背景的认识,例如DNA复制、转录和染色体分离——这些过程对于预防肿瘤发生至关重要。