拓扑异构酶Ⅱ的结构、功能及作用机制研究进展

Structural,mechanistic and functional insights into topoisomerase Ⅱ

拓扑异构酶是存在于细胞核内的一类酶,它们能够催化DNA链的断裂和结合,从而调控DNA的拓扑状态,在基因复制、转录、重组、修复和染色体重塑过程中参与了DNA超螺旋结构模板的调节。拓扑异构酶通过催化切断DNA链的磷酸二酯键,产生DNA缺口而发挥作用,这种缺口可以改变DNA分子的拓扑结构,从而解决DNA缠结状态这一问题。在哺乳动物中,主要存在I型和II型两种拓扑异构酶。拓扑异构酶I(type I topoisomerase,Top1)催化产生DNA分子上的单链缺口,而拓扑异构酶II(type II topoisomerase,Top2)则催化产生DNA分子上的双链缺口。Top2在哺乳动物中又分为α亚型和β亚型。其中,Top2α的功能主要与细胞的增殖和多潜能性相关,而Top2β在神经发育中具有重要作用。本文就Top2的结构、功能和作用机制的相关研究进展作一综述。

Topoisomerases are nuclear enzymes that regulate the overwinding or underwinding of DNA helix during replication,transcription,recombination,repair,and chromatin remodeling. These enzymes perform topological transformations by providing a transient DNA break,through which the unique problems of DNA entanglement that occur owing to unwinding and rewinding of the DNA helix can be resolved. In mammals,topoisomerases are classified into two types,type I topoisomerase（Top1） and type II topoisomerase（Top2）,depending on the number of strands cut in one round of action. Top1 induces single-strand breaks in DNA,and Top2 induces double-strand breaks. In cells from vertebrate species,there are two forms of Top2,designated alpha and beta. Top2α is involved in the cellular proliferation and pluripotency,while Top2β plays key roles in neurodevelopment. In this review,we cover recent advances in structural,mechanistic and functional insights into Top2.