SUMO-1 conjugation to topoisomerase I: A possible repair response to topoisomerase-mediated DNA damage
SUMO-1 conjugation to topoisomerase I: A possible repair response to topoisomerase-mediated DNA damage
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DOI：
10.1073/pnas.080536597
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发表时间：
2000-04-11
影响因子：
11.1
通讯作者：
Liu, LF
中科院分区：
文献类型：
--
作者：
Mao, Y;Sun, M;Liu, LF
拓扑异构酶1（topoisomerase 1，TOP 1）的泛素/26 S蛋白酶体依赖性降解被认为是TOP 1介导的DNA损伤的独特修复反应。在目前的研究中，我们表明，哺乳动物细胞或酵母细胞表达人DNA TOP 1与喜树碱（CPT）的治疗诱导共价修饰的TOP 1的SUMO-1/Smt 3 p，泛素样蛋白。该结论基于以下观察：（i）CPT诱导的哺乳动物DNA TOP 1缀合物与表达人DNA TOP 1的酵母以及哺乳动物细胞中的SUMO-1/Smt 3 p特异性抗体交叉反应。(ii)TOP1缀合物的形成显示依赖于UBC 9，SUMO-1/Smt 3 p的E2酶。(iii)（iv）表达人DNA TOP 1的Ubc 9突变酵母细胞对CPT高度敏感，提示UBC 9/SUMO-1可能参与TOP 1介导的DNA损伤修复。
Ubiquitin/26S proteasome-dependent degradation of topoisomerase 1 (TOP1) has been suggested to be a unique repair response to TOP1-mediated DNA damage. In the current study, we show that treatment of mammalian cells or yeast cells expressing human DNA TOP1 with camptothecin (CPT) induces covalent modification of the TOP1 by SUMO-1/Smt3p, a ubiquitin-like protein. This conclusion is based on the following observations: (i) Mammalian DNA TOP1 conjugates induced by CPT were cross-reactive with SUMO-1/Smt3p-specific antibodies both in yeast expressing human DNA TOP1 as well as mammalian cells. (ii) The formation of TOP1 conjugates was shown to be dependent on UBC9, the E2 enzyme for SUMO-1/Smt3p. (iii) TOP1 physically interacts with UBC9, (iv) Ubc9 mutant yeast cells expressing human DNA TOP1 was hypersensitive to CPT, suggesting that UBC9/SUMO-1 may be involved in the repair of TOP1-mediated DNA damage.