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拓扑异构酶II的结构、功能及作用机制研究进展

秦尚尧, 袁一旻, 胡昕, 孙秀, 苏志达^*

第二军医大学神经科学研究所，分子神经生物学教育部重点实验室，上海 200433

摘要

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。

关键词： 拓扑异构酶II; 分子结构 ; 功能 ; 作用机制

分类号：R329

Structural, mechanistic and functional insights into topoisomerase II

QIN Shang-Yao, YUAN Yi-Min, HU Xin, SUN Xiu, SU Zhi-Da^*

Institute of Neuroscience and Key Laboratory of Molecular Neurobiology of Ministry of Education, Second Military Medical University, Shanghai 200433, China

Abstract

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.

Key words: type II topoisomerase; molecular structure ; function ; mechanism

收稿日期：2015-09-19　　录用日期：2015-10-22

通讯作者：苏志达　　E-mail: suzhida@smmu.edu.cn

引用本文：

秦尚尧, 袁一旻, 胡昕, 孙秀, 苏志达. 拓扑异构酶II的结构、功能及作用机制研究进展[J]. 生理学报 2016; 68 (1): 98-106.

QIN Shang-Yao, YUAN Yi-Min, HU Xin, SUN Xiu, SU Zhi-Da. Structural, mechanistic and functional insights into topoisomerase II. Acta Physiol Sin 2016; 68 (1): 98-106 (in Chinese with English abstract).