SUMO-1 conjugation to human DNA topoisomerase II isozymes
SUMO-1 conjugation to human DNA topoisomerase II isozymes
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DOI：
10.1074/jbc.m001831200
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发表时间：
2000-08-25
影响因子：
4.8
通讯作者：
Liu, LF
中科院分区：
文献类型：
--
作者：
Mao, Y;Desai, SD;Liu, LF
喜树碱诱导的拓扑异构酶I介导的DNA损伤已显示诱导快速小泛素相关修饰物（SUMO）-1与拓扑异构酶I缀合。在目前的研究中，我们表明，拓扑异构酶II介导的DNA损伤诱导的替尼泊苷（VM-26）的结果在形成高分子量共轭物的拓扑异构酶II α和II β同工酶在HeLa细胞。这些缀合物的免疫学表征表明，拓扑异构酶II α和II β同工酶都与SUMO-1缀合。拓扑异构酶II和SUMO-1/UBC 9之间的物理相互作用的证明也支持SUMO-1/UBC 9参与拓扑异构酶II同工酶的修饰。令人惊讶的是，ICRF-193，它不诱导拓扑异构酶II介导的DNA损伤，但陷阱拓扑异构酶II成环状钳构象，也显示诱导类似的SUMO-1共轭拓扑异构酶II同工酶。此外，我们表明，氧化和热休克应激，这可能会导致蛋白质损伤，迅速增加核SUMO-1结合物。这些研究提出了一个问题，即SUMO-1与拓扑异构酶的结合是DNA损伤反应的间接结果还是蛋白质构象变化的直接结果。
Topoisomerase I-mediated DNA damage induced by camptothecin has been shown to induce rapid small ubiquitin-related modifier (SUMO)-1 conjugation to topoisomerase I. In the current study, we show that topoisomerase II-mediated DNA damage induced by teniposide (VM-26) results in the formation of high molecular weight conjugates of both topoisomerase II alpha and II beta isozymes in HeLa cells. Immunological characterization of these conjugates suggests that both topoisomerase II alpha and II beta isozymes are conjugated to SUMO-1, The involvement of SUMO-1/UBC9 in the modification of topoisomerase II isozymes is also supported by the demonstration of physical interaction between topoisomerase II and SUMO-1/UBC9. Surprisingly, ICRF-193, which does not induce topoisomerase II-mediated DNA damage but traps topoisomerase II into a circular clamp conformation, is also shown to induce similar SUMO-1 conjugation to topoisomerase II isozymes. In addition, we show that both oxidative and heat shock stresses, which can cause protein damage, rapidly increase nuclear SUMO-1 conjugates. These studies raise the question on whether SUMO-1 conjugation to topoisomerases is an indirect result of a DNA damage response or a direct result because of protein conformational changes.