SUMO modification of DNA topoisomerase II: trying to get a CENse of it all.
SUMO modification of DNA topoisomerase II: trying to get a CENse of it all.
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DOI：
10.1016/j.dnarep.2009.01.004
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发表时间：
2009-04-05
期刊：
影响因子：
3.8
通讯作者：
Bachant, Jeff
中科院分区：
文献类型：
--
作者：
Lee, Ming-Ta;Bachant, Jeff
关键词：
DNA拓扑异构酶II（topoisomerase II，topo II）是染色体结构和功能的重要决定因素，它的作用是解决DNA重组、转录、复制和分离中的拓扑问题。特别是，拓扑异构酶II的独特的decatenating活动所需的姐妹染色单体在有丝分裂中分离和分开。拓扑异构酶Ⅱ在有丝分裂染色体上表现出动态定位模式，在分裂后期之前积累在着丝粒和轴向染色体核心处。在从酵母到人类的生物体中，一部分拓扑异构酶II是有丝分裂细胞中SUMO结合的目标，在这里，我们回顾了我们目前对这种修饰的意义的理解。正如我们将看到的，一个正在形成的共识是，在后生动物中，拓扑异构酶II在着丝粒处积累需要SUMO修饰，并且在缺乏这种调节的情况下，染色体不分离、分离错误和非整倍体的频率升高。SUMO如何控制topo II的潜在分子机制尚不清楚。最后，然而，我们将评估两种可能的解释：一种是SUMO促进酶周转，第二种是SUMO作为topo II染色体运输的定位标签。
DNA topoisomerase II (topo II) is an essential determinant of chromosome structure and function, acting to resolve topological problems inherent in recombining, transcribing, replicating and segregating DNA. In particular, the unique decatenating activity of topo II is required for sister chromatids to disjoin and separate in mitosis. Topo II exhibits a dynamic localization pattern on mitotic chromosomes, accumulating at centromeres and axial chromosome cores prior to anaphase. In organisms ranging from yeast to humans, a fraction of topo II is targeted for SUMO conjugation in mitotic cells, and here we review our current understanding of the significance of this modification. As we shall see, an emerging consensus is that in metazoans SUMO modification is required for topo II to accumulate at centromeres, and that in the absence of this regulation there is an elevated frequency of chromosome non-disjunction, segregation errors, and aneuploidy. The underlying molecular mechanisms for how SUMO controls topo II are as yet unclear. In closing, however, we will evaluate two possible interpretations: one in which SUMO promotes enzyme turnover, and a second in which SUMO acts as a localization tag for topo II chromosome trafficking.
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