The N-terminal domain anchors human topoisomerase I at fibrillar centers of nucleoli and nucleolar organizer regions of mitotic chromosomes
The N-terminal domain anchors human topoisomerase I at fibrillar centers of nucleoli and nucleolar organizer regions of mitotic chromosomes
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DOI：
10.1074/jbc.m204738200
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发表时间：
2002-09-27
影响因子：
4.8
通讯作者：
Mielke, C
中科院分区：
文献类型：
--
作者：
Christensen, MO;Barthelmes, HU;Mielke, C
DNA拓扑异构酶I释放由DNA转录产生的扭转应力。原则上，这种活性是核质中mRNA合成和核仁中rRNA合成所必需的。然而，拓扑异构酶I主要是核仁蛋白。目前的观点认为，这种偏好是由酶的N-末端结构域触发的，这构成了核仁输入信号。与这种观点相矛盾，我们在这里表明，拓扑异构酶I的各种片段的核仁积累与它们在这间室的流动性较小，而不是与N-末端结构域是完整的或存在。因此，N-末端结构域不太可能是核仁输入信号。我们发现，它，而不是作为一个适配器，锚定在有丝分裂染色体的核仁和核仁组织者区的纤维中心的拓扑异构酶I的亚群。因此，它提供了拓扑异构酶I与rDNA和RNA聚合酶I的稳定缔合，其在整个细胞周期期间维持在活细胞中。
DNA topoisomerase I releases torsion stress created by DNA transcription. In principle, this activity is required in the nucleoplasm for mRNA synthesis and in the nucleoli for rRNA synthesis. Yet, topoisomerase I is mostly a nucleolar protein. Current belief holds that this preference is triggered by the N-terminal domain of the enzyme, which constitutes a nucleolar import signal. Contradicting this view, we show here that nucleolar accumulation of various fragments of topoisomerase I is correlated with their lesser mobility in this compartment and not with the N-terminal domain being intact or present. Therefore, the N-terminal domain is not likely a nucleolar import signal. We show that it rather serves as an adaptor that anchors a subpopulation of topoisomerase I at fibrillar centers of nucleoli and nucleolar organizer regions of mitotic chromosomes. Thus, it provides a steady association of topoisomerase I with the rDNA and with RNA polymerase I, which is maintained in a living cell during the entire cell cycle.